Isoptin 80

Package leaflet: Information for the patient

Warning! Keep this leaflet! Information on the immediate packaging in a foreign language.
Isoptin 80 (Isoptin), 80 mg, film-coated tablets
Verapamili hydrochloridum
Isoptin 80 and Isoptin 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 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. It may harm someone else, even if their symptoms are the same.
• If you experience any adverse effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Table of contents:

1. What Isoptin 80 is and what it is used for
2. What you need to know before taking Isoptin 80
3. How to take Isoptin 80
4. Possible side effects
5. How to store Isoptin 80
6. Contents of the pack and other information

1. What Isoptin 80 is and what it is used for

Isoptin 80 is available as film-coated tablets containing 80 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
concomitant increase in heart rate. In individuals with normal blood pressure, the drug
does not produce significant hypotensive effects.
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 80 is indicated for use in adults, children, and adolescents 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-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 80

When not to use Isoptin 80:

• 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 cardiac pacemaker)
• in sick sinus syndrome (except in patients with a functioning cardiac pacemaker)
• in heart failure with reduced ejection fraction below 35% and/or pulmonary capillary wedge pressure above 20 mmHg (unless secondary to a supraventricular tachyarrhythmia that responds 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 80, 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 80 and other medicines
Inform your doctor about all medicines currently or recently taken, 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)
• 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-_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 80"
• metformin (used in the treatment of diabetes). Verapamil may reduce the glucose-lowering effect of metformin.

Isoptin 80 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 advised 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 80 and lithium, even when serum lithium concentrations remained unchanged or increased. However, adding Isoptin 80 has also been associated with decreased serum lithium concentrations in patients on chronic oral lithium therapy. Patients receiving both drugs should be closely monitored.

Neuromuscular blocking agents
The drug may potentiate the effects of neuromuscular blocking agents (both non-depolarizing and depolarizing types). Dose reduction of Isoptin 80 and/or the neuromuscular blocking agent may be necessary when these drugs are used together.

Acetylsalicylic acid
Increased tendency to bleeding.

Ethanol
Increased plasma ethanol concentration.

HMG-CoA reductase inhibitors (statins)
In patients receiving Isoptin 80, 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 Isoptin 80 is initiated in patients already taking an HMG-CoA reductase inhibitor (e.g. simvastatin, atorvastatin, or lovastatin), consider reducing the statin dose and subsequently adjusting 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 adequate 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 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 80 may affect reaction ability to such an extent that it impairs the ability to drive vehicles, operate machinery, or work under 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 80 contains sodium
Isoptin 80 contains less than 1 mmol (23 mg) of sodium per tablet; therefore, the medicine is considered "sodium-free".

3. How to use Isoptin 80

This medicine should always be used as directed by the physician. In case of doubt, consult your
doctor or pharmacist.
The following preparations are available on the market: Isoptin 40 (40 mg), Isoptin 80 (80 mg).
The dose 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,
the drug must not be discontinued abruptly. Gradual dose reduction is recommended.
Isoptin 80 should be used in patients who require a satisfactory response 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, or alternatively Isoptin SR or Isoptin SR-E 240, should
be used.
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 three divided doses.
Angina pectoris, 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 verapamil hydrochloride per day in two or three divided
doses.
From 6 to 14 years of age: 80 mg to 360 mg 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 stronger and prolonged drug effects. 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).
Use of a higher than recommended dose of Isoptin 80
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 as a result of 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 parenteral 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. 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 80
Do not take a double dose to make up for a missed dose.
Discontinuation of Isoptin 80
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 occurring adverse reactions were: headache, dizziness, gastrointestinal disturbances: nausea, constipation and abdominal pain, as well as bradycardia, tachycardia, palpitations, 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, 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, sinoatrial block, 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

Post-marketing reports have included one case of paralysis (quadriparesis) following concomitant use of verapamil and colchicine.
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 of 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 enables further information on the safety of the medicine to be collected.

5. How to store the medicine Isoptin 80

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 required. This will help protect the environment.

6. Contents of the pack and other information

What Isoptin 80 contains
The active substance is verapamil hydrochloride. Each film-coated tablet contains 80 mg of verapamil hydrochloride.
The other components 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 80 looks like and contents of the pack
Isoptin 80 is available in packs containing: 40 tablets, 50 tablets.
PVC/Aluminium blisters 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., 15 km. Athinon Marathonos Avenue, 153 44 Pallini Attiki, 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: 16447/26-02-2013
8571/06-02-2007
Parallel Import Licence Number: 92/25