Staveran 40

Leaflet accompanying the packaging: patient information

STAVERAN 40, 40 mg, coated tablets

STAVERAN 80, 80 mg, coated tablets

STAVERAN 120, 120 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 them, even if their symptoms are the same as yours.
• If the patient experiences any side effects, including any not listed in this leaflet, they should tell their doctor. See section 4.

Table of contents of the leaflet

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

1. What is Staveran and what is it used for

Staveran is available in the form of coated tablets containing 40 mg, 80 mg or 120 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 reduced peripheral resistance without a significant 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 disorders, is based on the slowing of conduction in the atrioventricular node. As a result, depending on the type of rhythm disorder, 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.

Staveran is indicated for use in adults, children and adolescents for the prevention and/or 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 pectoris after myocardial infarction without heart failure, when beta-adrenergic blockers are not indicated,
• heart rhythm disorders, 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 Staveran

When not to take Staveran

• 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 atrioventricular block II° or III° (except for patients with a functioning pacemaker),
• in sick sinus syndrome (except for patients with a functioning pacemaker),
• in heart failure with reduced ejection fraction below 35% and/or pulmonary capillary wedge pressure above 20 mmHg (if not secondary to supraventricular tachycardia responding to verapamil treatment),
• in atrial fibrillation/flutter with accessory conduction pathway (e.g. Wolff-Parkinson-White syndrome [WPW], Lown-Ganong-Levine syndrome [LGL]). In these patients, there is a risk of ventricular tachyarrhythmia, including ventricular fibrillation,
• if the patient is taking intravenously administered beta-adrenergic blockers,
• if the patient is taking medicines containing ivabradine (medicines used to treat certain heart conditions).

Warnings and precautions

Before starting treatment with Staveran, discuss it with your doctor.
Particular caution should be exercised in patients:

• with acute myocardial infarction complicated by bradycardia (less than 50 beats per minute), significant hypotension or left ventricular dysfunction,
• with heart block, atrioventricular block I°, bradycardia, asystole,
• taking antiarrhythmic drugs,
• taking beta-adrenergic blockers,
• taking digoxin,
• with heart failure with ejection fraction above 35%,
• with hypotension (systolic blood pressure below 90 mmHg),
• taking statins,
• with neuromuscular transmission disorders [myasthenia gravis, Lambert-Eaton syndrome, late stages of Duchenne muscular dystrophy],
• with renal dysfunction,
• with hepatic dysfunction.

Staveran and other medicines

Tell your doctor or pharmacist about all medicines you are taking, have recently taken or might 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. glibenclamide),
• drugs for gout (e.g. colchicine),
• infections (e.g. clarithromycin, erythromycin, rifampicin, telithromycin),
• anticancer drugs (e.g. doxorubicin),
• barbiturates (e.g. phenobarbital),
• benzodiazepines and other anxiolytics (e.g. buspirone, midazolam),
• beta-adrenergic blockers (e.g. metoprolol, propranolol),
• cardiac glycosides (e.g. digitoxin, digoxin),
• H2 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 (e.g. sulfinpyrazone),
• dabigatran (a medicine used to prevent blood clots).

Additional information on some interactions is provided below.
Antiviral medicines for human immunodeficiency virus (HIV)
Ritonavir may increase verapamil plasma concentrations, enhancing its effect. Caution should be exercised when these medicines 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 verapamil and lithium without changes or with increased lithium serum concentrations. However, the addition of verapamil also resulted in decreased lithium serum concentrations in patients chronically receiving oral fixed doses of lithium. Patients receiving both medicines should be closely monitored.
Medicines blocking neuromuscular transmission
The medicine may enhance the effect of medicines blocking neuromuscular transmission (curare-like and depolarizing medicines). It may be necessary to reduce the dose of Staveran and/or the dose of the medicine blocking neuromuscular transmission when these medicines are used together.
Acetylsalicylic acid
Increased tendency to bleeding.
Ethyl alcohol
Increased ethanol plasma concentrations.
Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins)
In patients taking Staveran, 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 dose of the statin and then re-adjust it, taking into account the serum cholesterol concentration.
The likelihood of an interaction with fluvastatin, pravastatin or rosuvastatin with the medicine is lower.
Hypotensive, diuretic and vasodilating medicines
Enhanced hypotensive effect.
Metformin
Verapamil may reduce the effect of metformin on glucose levels.

Staveran with food, drinks and alcohol

Interactions with grapefruit juice and products containing St. John's wort extract are also possible.

Pregnancy and breastfeeding

If the patient is pregnant or breastfeeding, thinks she may be pregnant or plans to have a child, she should consult a doctor or pharmacist before taking this medicine.
There are no data on the use of the medicine in pregnant women, and therefore the medicine can be used during 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 using machines

In some patients, Staveran may affect their ability to react to such an extent that it impairs their ability to drive vehicles and operate machinery or work in hazardous conditions. This occurs especially during the initial treatment period, during dose increase, when switching from another medicine, and when consuming alcohol. The medicine may increase blood alcohol concentrations and delay its elimination.
For this reason, the effect of alcohol may be enhanced.

Staveran contains lactose monohydrate

If the patient has previously been diagnosed with intolerance to some sugars, the patient should contact their doctor before taking the medicine.

Staveran 40 contains orange yellow S (E110), Staveran 80 contains orange yellow S (E110) and Staveran 120 contains quinoline yellow (E104)

The medicine may cause allergic reactions.

3. How to take Staveran

This medicine should always be taken as directed by the doctor. In case of doubts, consult a doctor.
The dose of the medicine should be selected 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 use, the daily dose should not exceed 480 mg, while during short-term use, a higher dose may be used. The duration of treatment is unlimited. After long-term use, the medicine should not be abruptly discontinued. Gradual dose reduction is recommended.
Staveran 40 should be used in patients who are expected to respond satisfactorily to small doses (e.g. patients with liver failure or the elderly). In patients requiring higher doses (e.g. 240 mg to 480 mg of verapamil hydrochloride per day), Staveran 80 or Staveran 120 should be used.
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 heart 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 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 a varying degree, depending on the degree of liver failure, which makes the medicine act stronger and longer. Therefore, particular caution should be exercised when determining the dose in patients with liver failure, and during the initial treatment period, small doses should be administered (see Warnings and precautions).
Administration
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.

Taking a higher dose of Staveran than recommended

In case of taking a higher dose of the medicine than recommended, contact a doctor or report to the emergency department of the nearest hospital immediately.
Overdose symptoms include:
Hypotension, bradycardia, slowing of conduction up to high-degree atrioventricular block and sinus arrest,
Hyperglycemia, stupor, metabolic acidosis. Overdose has led to death.
Treatment
In overdose, supportive treatment should be applied, individually tailored. In the treatment of intentional overdose, beta-adrenergic stimulation and/or parenteral calcium (calcium chloride) have been effectively used. In case of clinically significant hypotension or high-degree atrioventricular block, vasopressor agents or cardiac pacing should be used, respectively.
In case of asystole, standard procedures should be applied, including beta-adrenergic stimulation (e.g. isoprenaline hydrochloride), other vasopressor agents or cardiopulmonary resuscitation. Verapamil hydrochloride cannot be removed from the body by hemodialysis.

Missing a dose of Staveran

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

Stopping treatment with Staveran

After long-term use, the medicine should not be abruptly discontinued. Gradual dose reduction is recommended.
In case of any further doubts regarding the use of this medicine, consult a doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine 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 presented according to the frequency classification:
Frequent(occurring in less than 1 in 10 patients):

• central dizziness, headache,
• bradycardia,
• flushing, hypotension,
• constipation, nausea,
• peripheral edema.

Uncommon(occurring in less than 1 in 100 patients):

• palpitations, tachycardia,
• abdominal pain, diarrhea,
• fatigue.

Rare(occurring in less than 1 in 1,000 patients):

• paresthesia, muscle tremors,
• sleepiness,
• tinnitus,
• vomiting, dry mouth,
• excessive sweating.

Side effects with unknownfrequency (frequency cannot be determined based on available data):

• hypersensitivity reactions,
• extrapyramidal disorders, seizures,
• hyperkalemia,
• visual disturbances,
• peripheral dizziness,
• atrioventricular block (I°, II°, III°), heart failure, sinus arrest, sinus bradycardia, asystole,
• bronchospasm, dyspnea, pulmonary edema,
• abdominal discomfort, gingival hyperplasia, intestinal obstruction,
• angioedema, Stevens-Johnson syndrome, erythema multiforme, alopecia, pruritus, urticaria, rash, erythematous rash,
• arthralgia, muscle weakness, myalgia,
• renal failure, frequent urination,
• erectile dysfunction, galactorrhea, gynecomastia,
• increased prolactin levels in the blood, increased liver enzyme activity, occurrence of liver cell damage symptoms.

After the medicine was placed on the market, one case of paralysis (quadriparesis) was reported after concomitant use of verapamil and colchicine.

Reporting side effects

If side effects occur, including any not listed in the leaflet, the doctor, pharmacist or nurse should be informed. 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
Aleje Jerozolimskie 181C
02-222 Warsaw
Phone: +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 Staveran

The medicine should be stored out of sight and reach of children.
Store in the original packaging to protect from light. Do not store above 25°C.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the month.
The inscription on the packaging after the abbreviation EXP means the expiry date, and after the abbreviation Lot/LOT means the batch number.
Medicines should not be disposed of via wastewater or household waste. Ask your 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 Staveran contains:

• The active substance of the medicine is verapamil hydrochloride. Each tablet contains 40 mg, 80 mg or 120 mg of verapamil hydrochloride.
• Other ingredients are: Tablet core: gelatin, crystalline cellulose, lactose monohydrate, anhydrous colloidal silica, magnesium stearate, talc, potato starch Tablet coating: hypromellose, macrogol 6000, titanium dioxide (E171), talc, orange yellow S (E110) (Staveran 40), orange yellow S (E110) (Staveran 80), quinoline yellow (E104) (Staveran 120).

What Staveran looks like and contents of the packaging

Staveran 40 mg, are orange, round, biconvex coated tablets.
Staveran 80 mg, are orange, round, biconvex coated tablets with a score line on one side.
Staveran 120 mg, are yellow, round, biconvex coated tablets with a score line on one side.
One packaging contains 20 or 60 tablets.
Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder

Polpharma S.A.
Pelplińska 19, 83-200 Starogard Gdański
phone: +48 22 364 61 01

Manufacturer

Polpharma S.A.
Medana division in Sieradz
Władysława Łokietka 10, 98-200 Sieradz
Polpharma S.A.
Production Plant in Nowa Dęba
Metalowca 2
39-460 Nowa Dęba

Date of last revision of the leaflet: