Isoptin 40

Leaflet accompanying the packaging: patient information

Isoptin 40, 40 mg, coated tablets

Isoptin 80, 80 mg, coated tablets

Verapamil hydrochloride

Read the leaflet carefully before taking the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• In case of any doubts, consult a doctor or pharmacist.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including any side effects not listed in the leaflet, they should tell their doctor or pharmacist. See section 4.

Table of contents of the leaflet:

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

1. What is Isoptin and what is it used for

Isoptin is available in the form of coated tablets containing 40 mg or 80 mg of the active substance - verapamil hydrochloride. Verapamil hydrochloride is a selective calcium antagonist acting directly on the heart muscle.
The action of the medicine is based on the inhibition of calcium ion passage through the cell membrane to the heart muscle cells and blood vessel muscle cells.
The medicine has antihypertensive and antiarrhythmic effects.
The antihypertensive effect of the medicine is the result of a decrease in peripheral resistance without a simultaneous increase in heart rate. In the case of normal blood pressure, the medicine does not have a significant hypotensive effect.
The antiarrhythmic effect, especially in the case of supraventricular rhythm disturbances, is based on the slowing of conduction in the atrioventricular node. As a result, depending on the type of rhythm disturbance, there is a restoration of sinus rhythm and/or normalization of ventricular contractions. The medicine does not change the normal heart rate or only slightly reduces it.
Isoptin is indicated for use in adults, children, and adolescents for the treatment of:

• hypertension
• coronary heart 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 after myocardial infarction without heart failure, when beta-adrenergic blockers are not indicated
• arrhythmias, such as:
• paroxysmal supraventricular tachycardia, atrial fibrillation/flutter with rapid atrioventricular conduction (except for Wolff-Parkinson-White syndrome [WPW] or Lown-Ganong-Levine syndrome [LGL])

2. Important information before taking Isoptin

When not to take Isoptin

Warnings and precautions

Before starting treatment with Isoptin, the patient should discuss it with their doctor.
Special caution should be exercised in patients:
˗˗˗˗˗˗˗˗˗˗

Isoptin and other medicines

The patient should tell their doctor about all medicines they are currently taking or have recently taken, including those they plan to take.
Interactions with verapamil are possible with the following medicines:

• alpha-adrenergic blockers (e.g., prazosin, terazosin)
• antiarrhythmic drugs (e.g., flecainide, quinidine)
• bronchodilators (e.g., theophylline)
• antiepileptic and anticonvulsant drugs (e.g., carbamazepine, phenytoin)
• antidepressants (e.g., imipramine)
• antidiabetic drugs (e.g., gliburyde)
• drugs for gout (e.g., colchicine)
• antibiotics (e.g., clarithromycin, erythromycin, rifampicin, telithromycin)
• anticancer drugs (e.g., doxorubicin)
• barbiturates (e.g., phenobarbital)
• benzodiazepines and other anxiolytic drugs (e.g., buspirone, midazolam)
• beta-adrenergic blockers (e.g., metoprolol, propranolol)
• cardiac glycosides (e.g., digitoxin, digoxin)
• H receptor antagonists (e.g., cimetidine)
• immunomodulating and immunosuppressive drugs (e.g., cyclosporine, everolimus, sirolimus, tacrolimus)
• lipid-lowering drugs (e.g., atorvastatin, lovastatin, simvastatin)
• serotonin receptor agonists (e.g., almotriptan)
• drugs increasing uric acid excretion in urine (e.g., sulfinpyrazone) - dabigatran (anticoagulant) and direct-acting oral anticoagulants - ivabradine (used in the treatment of heart diseases), see "When not to take Isoptin" - metformin (used in the treatment of diabetes). Verapamil may reduce the effect of metformin in reducing glucose levels.

Isoptin with food and drink

Interactions with grapefruit juice and products containing St. John's wort extract are also possible.
Additional information on some interactions is provided below.
Antiviral drugs against human immunodeficiency virus (HIV)
Ritonavir may increase verapamil plasma levels, enhancing its effect. Caution should be exercised when these drugs are used together, and if necessary, the verapamil dose should be reduced.
Lithium
There have been reports of increased lithium sensitivity (neurotoxicity) during concomitant treatment with Isoptin and lithium without changes or with increased lithium serum levels. However, the addition of Isoptin also resulted in decreased lithium serum levels in patients chronically receiving oral fixed doses of lithium. Patients receiving both drugs should be closely monitored.
Drugs blocking neuromuscular transmission
The medicine may enhance the effect of drugs blocking neuromuscular transmission (curare-like and depolarizing drugs). It may be necessary to reduce the dose of Isoptin and/or the dose of the drug blocking neuromuscular transmission when these drugs are used together.
Acetylsalicylic acid
Increased tendency to bleeding.
Ethyl alcohol
Increased ethanol plasma levels.
Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins)
In patients taking Isoptin, treatment with hydroxymethylglutaryl-coenzyme A reductase inhibitors (e.g., simvastatin, atorvastatin, or lovastatin) should be started with the lowest possible dose, which is then adjusted by gradual increase.
If the use of the medicine is started in patients already taking a hydroxymethylglutaryl-coenzyme A reductase inhibitor (e.g., simvastatin, atorvastatin, or lovastatin), it is recommended to consider reducing the statin dose and then readjust it based on serum cholesterol levels.
The likelihood of an interaction with fluvastatin, pravastatin, or rosuvastatin is lower.
Hypotensive, diuretic, and vasodilating drugs
Enhanced hypotensive effect.

Pregnancy and breastfeeding

If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a child, they should consult their doctor before taking this medicine.
There are no data on the use of the medicine in pregnant women, and therefore, the medicine can be used in pregnancy only if it is absolutely necessary.
The medicine passes into breast milk in a small percentage. The risk to newborns and infants cannot be excluded. However, due to the possibility of severe side effects in breastfed infants, the medicine can be used during breastfeeding only if it is essential for the mother's health.

Driving and operating machinery

In some patients, Isoptin may affect their ability to react to such an extent that it impairs their ability to drive vehicles, operate machinery, or work in hazardous conditions. This is especially true during the initial treatment period, when increasing the dose, when switching from another medicine, and when consuming alcohol. The medicine may increase ethanol plasma levels and delay its elimination. Therefore, the effect of alcohol may be enhanced.

Isoptin contains sodium

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

3. How to take Isoptin

This medicine should always be taken according to the doctor's recommendations. In case of doubts, the patient should consult their doctor or pharmacist.
The dose of the medicine should be adjusted individually, depending on the severity of the disease. Long-term clinical experience confirms that in all indications, the daily dose is usually between 240 mg and 360 mg. During long-term treatment, the daily dose should not exceed 480 mg, while in short-term treatment, a higher dose can be used. The duration of treatment is unlimited. After long-term treatment, the medicine should not be stopped abruptly. A gradual reduction in dose is recommended.
Isoptin 40 coated tablets 40 mg should be used in patients who are expected to respond satisfactorily to small doses (e.g., patients with liver failure or elderly patients). In patients requiring higher doses (e.g., 240 mg to 480 mg of verapamil hydrochloride per day), Isoptin 80 or Isoptin SR or Isoptin SR-E 240 should be used.
Oral administration. The tablet should be swallowed whole (not sucked or chewed), with a sufficient amount of liquid, preferably during or immediately after a meal.
Adults and adolescents over 50 kg of body weight
Hypertension: 120 mg to 480 mg per day in three divided doses.
Coronary heart 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 arrhythmias)
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 dysfunction
When using the medicine in patients with renal dysfunction, caution should be exercised, and the patient's condition should be closely monitored.
Hepatic dysfunction
In patients with liver failure, the metabolism of the medicine is impaired to varying degrees, depending on the degree of liver failure, which makes the medicine act stronger and longer. Therefore, special caution should be exercised when determining the dose in patients with liver failure, and small doses should be administered during the initial treatment period (see "Warnings and precautions").

Overdose of Isoptin

Symptoms
Hypotension, bradycardia, slowing of conduction up to high-degree atrioventricular block and sinus arrest, hyperglycemia, stupor, metabolic acidosis, acute respiratory failure. Overdose has led to death.
Treatment
In case of overdose, supportive treatment should be applied, individually tailored. In the treatment of intentional overdose of the medicine taken orally, beta-adrenergic stimulation and/or parenteral calcium (calcium chloride) have been effectively used. In case of clinically significant reactions such as hypotension or high-degree atrioventricular block, vasopressor drugs or cardiac pacing should be used, respectively.
In case of asystole, standard procedures should be applied, including beta-adrenergic stimulation (e.g., isoproterenol hydrochloride), other vasopressor drugs, or cardiopulmonary resuscitation. Verapamil hydrochloride cannot be removed from the body by hemodialysis.

Missed dose of Isoptin

A double dose should not be taken to make up for a missed dose.

Stopping treatment with Isoptin

After long-term treatment, the medicine should not be stopped abruptly. A gradual reduction in dose is recommended.

4. Possible side effects

Like all medicines, Isoptin can cause side effects, although not everybody gets them.
The most common side effects were: headache, dizziness, gastrointestinal disorders: nausea, constipation, and abdominal pain, as well as bradycardia, tachycardia, palpitations, hypotension, flushing, peripheral edema, and fatigue.
Side effects are listed below by system organ class:
Common(in 1 to 10 patients out of 100):
˗
central dizziness, headache
˗
bradycardia
˗
flushing, 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
˗
drowsiness
˗
tinnitus
˗
vomiting
˗
excessive sweating
Side effects with unknownfrequency (frequency cannot be estimated from available data):
˗
hypersensitivity reactions
˗
extrapyramidal disorders, seizures
˗
hyperkalemia
˗
peripheral dizziness
˗
atrioventricular block (I°, II°, III°), heart failure, sinus arrest, sinus bradycardia, asystole (cardiac arrest)
˗
bronchospasm, dyspnea
˗
abdominal discomfort, gingival hyperplasia, intestinal obstruction
˗
angioedema, Stevens-Johnson syndrome, erythema multiforme, alopecia, pruritus, urticaria, rash, erythematous rash
˗
arthralgia, muscle weakness, myalgia
˗
renal failure
˗
sexual dysfunction, galactorrhea, gynecomastia
˗
increased prolactin levels in blood, increased liver enzyme activity
One case of paresis (quadriparesis) has been reported after concomitant use of verapamil and colchicine.
If any of the side effects worsen or any side effects not listed in the leaflet occur, the patient should inform their doctor or pharmacist.
If side effects occur, including any side effects not listed in the leaflet, the patient should tell their doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety Monitoring 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
Side effects can also be reported to the marketing authorization holder.
Reporting side effects will help to gather more information on the safety of the medicine.

5. How to store Isoptin

The medicine should be stored out of sight and reach of children.
Do not use this medicine after the expiry date stated on the carton after "EXP" and on the blister after "EXP". The expiry date refers to the last day of the month.
Do not store above 25°C.
Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the packaging and other information

What Isoptin contains

The active substance of the medicine is verapamil hydrochloride 40 mg or 80 mg.
The excipients are: calcium hydrogen phosphate dihydrate, microcrystalline cellulose, colloidal anhydrous silica, sodium carmellose, magnesium stearate, and the tablet coating: hypromellose, sodium lauryl sulfate, macrogol 6000, talc, titanium dioxide (E171).

What Isoptin looks like and contents of the pack

Isoptin 40 is available in packs containing:
40 tablets
50 tablets
Al/PVC blister pack in a cardboard box.
Isoptin 80 is available in packs containing:
40 tablets (4 blisters of 10 tablets)
50 tablets (5 blisters of 10 tablets)
Al/PVC blister pack in a cardboard box.

Marketing authorization holder and manufacturer

Marketing authorization holder

Viatris Healthcare Sp. z o.o.
ul. Postępu 21B
02-676 Warsaw

Manufacturer

FAMAR A.V.E. ANTHOUSSA PLANT
Anthoussa Avenue 7
Anthoussa Attiki
15349, Greece
To obtain more detailed information, the patient should contact the marketing authorization holder:
Viatris Healthcare Sp. z o.o.
ul. Postępu 21B
02-676 Warsaw
Tel: (22) 546 64 00
Date of last revision of the leaflet:02/2024