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 the entire 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 doubts, 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 effects, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents:

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 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 a reduction in 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 40 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 myocardium), 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-adrenolytic agents are not indicated
• cardiac arrhythmias, such as:
• paroxysmal supraventricular tachycardia, atrial fibrillation/flutter with rapid ventricular response (excluding 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 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 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 40, discuss this with your doctor.
Special caution is required in patients:

• with acute myocardial infarction complicated by bradycardia, significant hypotension, or left ventricular dysfunction
• with cardiac conduction disorders, 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 40 and other medicines
Tell your doctor about all medicines you are currently taking or have recently taken, including those you plan to take.

Possible interactions between verapamil and 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)
• antineoplastic agents (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 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 (DOACs)
• 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 weaken 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 concentration, 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, with unchanged or increased serum lithium levels. However, adding Isoptin 40 has also been associated with decreased serum lithium levels 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 dose of the neuromuscular blocking agent when these drugs are used concomitantly.

Acetylsalicylic acid
Increased tendency to bleeding.

Ethanol (alcohol)
Increased plasma concentration of ethanol.

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 started 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 agents
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 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 40 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 especially 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 intensified.

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

3. How to use Isoptin 40

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

Isoptin, coated tablets, is available in the following strengths: 40 mg (Isoptin 40) or 80 mg (Isoptin 80).

The dosage must be individually adjusted according to 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 for short-term treatment. There is no limitation on the duration of treatment. After prolonged use, the drug must not be abruptly discontinued. Gradual dose reduction is recommended.

Isoptin 40 coated tablets 40 mg should be used in patients who are expected to respond adequately to low doses (e.g., patients with hepatic impairment or elderly patients). For 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 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 daily in three divided doses.
• Angina pectoris, paroxysmal supraventricular tachycardia, atrial fibrillation, and atrial flutter: 120 mg to 480 mg daily in three or four divided doses.

Special populations

Children and adolescents (only for cardiac rhythm disorders)

• Up to 6 years of age: 80 mg to 120 mg of verapamil hydrochloride daily in two or three divided doses.
• 6 to 14 years of age: 80 mg to 360 mg of verapamil hydrochloride daily in two, three, or four divided doses.

Renal function impairment

Caution should be exercised when administering this medicine to patients with impaired renal function, 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 increased and prolonged drug effects. Therefore, particular caution is required 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. Fatal outcomes have occurred following overdose.

Treatment

In case of overdose, supportive treatment tailored to the individual patient should be primarily administered. For 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 management should be applied, including β-adrenergic stimulation (e.g., isoprenaline hydrochloride), other vasopressor agents, 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 medicine should not be abruptly discontinued. Gradual dose reduction is recommended.

4. Possible adverse effects

Like all medicines, this medicine may cause adverse effects, although not everyone experiences them.
The most commonly occurring adverse effects 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 effects are listed below by system organ class:
Common (in 1 to 10 patients out of 100 patients):
˗ central dizziness, headaches
˗ bradycardia
˗ skin flushing with sensation of warmth, 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 effects occurring with unknown frequency (frequency cannot be
estimated from available data):
˗ hypersensitivity reactions
˗ extrapyramidal disorders, seizures
˗ hyperkalaemia
˗ peripheral dizziness
˗ atrioventricular block (1st, 2nd, 3rd degree), 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
After marketing authorisation, one case of paralysis (quadriparesis) has been reported following concomitant use of verapamil and colchicine.
If any of the adverse effects worsen or if any adverse effects not listed in this leaflet occur, consult a doctor or pharmacist.
Reporting of adverse effects
If any adverse effects occur, including any adverse effects
not listed in this leaflet, inform your doctor or pharmacist.
Adverse effects 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 181 C
02-222 Warsaw
Tel.: + 48 22 49 21 301 Fax: + 48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Reporting adverse effects allows collection of further information on the safety of the medicine.

5. How to store the medicine 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 required. This will help protect the environment.

6. Contents of the packaging and other information

What Isoptin 40 contains
The active substance is verapamil hydrochloride 40 mg.
The excipients are: calcium hydrogen phosphate dihydrate, microcrystalline cellulose, anhydrous colloidal silicon dioxide, sodium croscarmellose, magnesium stearate, and the tablet coating:
hypromellose 2910, sodium lauryl sulfate, polyethylene glycol 6000, purified talc, titanium dioxide (E 171).
What Isoptin 40 looks like and contents of the pack
Isoptin 40 is available in packs containing 40 or 50 film-coated tablets, in PVC/Al blisters, packed in a cardboard box.
For more detailed information, please contact the responsible entity or the parallel importer.
Marketing Authorisation Holder in Greece, the country of export:
BGP Proionta M.E.P.E
Ag. Dimitriou 63
174 56 Alimos
Greece
Manufacturer
Vianex S.A.
15 km. Athinon Marathonos Avenue
153 44 Pallini Attiki
Greece
Parallel importer:
Medezin Sp. z o.o.
ul. Zbąszyńska 3
91-342 Łódź
Repackaged by:
Medezin Sp. z o.o.
ul. Zbąszyńska 3
91-342 Łódź
CEFEA Sp. z o.o. Sp. komandytowa
ul. Działkowa 56
02-234 Warsaw
SHIRAZ PRODUCTIONS Sp. z o.o.
ul. Tymiankowa 24/28
95-054 Ksawerów
CANPOLAND SPÓŁKA AKCYJNA
ul. Beskidzka 190
91-610 Łódź
Greece Marketing Authorisation Number: 8571/06-02-2007
Parallel Import Licence Number: 382/22