Staveran 80

Patient Information Leaflet

STAVERAN 40, 40 mg, film-coated tablets
STAVERAN 80, 80 mg, film-coated tablets
STAVERAN 120, 120 mg, film-coated tablets
Verapamili hydrochloridum
Please read carefully the entire leaflet before using this medicine, as it contains
important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not share it with others. This medicine may harm other people, even if their symptoms are similar.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor. See section 4.

Table of Contents

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

1. What is Staveran and for what purposes is it used

Staveran is available as film-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 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 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, results from slowing conduction through the atrioventricular node. As a result, depending on the type of arrhythmia, sinus rhythm may be restored and/or ventricular rate normalized. The drug does not alter 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 artery disease (conditions characterized by insufficient oxygen supply to the myocardium), including:
• chronic stable angina pectoris,
• unstable angina pectoris (with increasing pain, pain at rest),
• Prinzmetal's angina,
• post-myocardial 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 atrioventricular conduction (excluding Wolff-Parkinson-White syndrome [WPW] or Lown-Ganong-Levine syndrome [LGL]).

2. Important information before using Staveran

When not to use 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 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 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 receiving intravenous beta-blocking agents,
• if the patient is taking drugs containing ivabradine (medicines used in the treatment of certain heart diseases).

Warnings and precautions
Before starting treatment with Staveran, discuss this with your doctor.
Particular caution is required in patients:

• with acute myocardial infarction complicated by bradycardia (less than 50 beats per minute), significant hypotension, or left ventricular dysfunction,
• with heart block, first-degree atrioventricular block, bradycardia, or asystole,
• taking antiarrhythmic drugs,
• taking β-adrenergic blocking agents,
• taking digoxin,
• with heart failure and 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 impairment,
• with hepatic impairment.

Staveran and other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take.
Verapamil may interact with the following medicines:

• α-adrenergic blocking 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. glibenclamide),
• antigout drugs (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 blocking agents (e.g. metoprolol, propranolol),
• cardiac glycosides (e.g. digitoxin, digoxin),
• H\textsubscript{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 (a medicine used to prevent blood clots).

Additional information on certain 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 verapamil dose should be reduced.
Lithium
Increased sensitivity to lithium (neurotoxicity) has been reported during concomitant treatment with verapamil and lithium, with unchanged or increased serum lithium concentrations. However, addition of verapamil has also led to 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 Staveran and/or the dose of the neuromuscular blocking agent when these drugs are used together.
Acetylsalicylic acid
Increased risk of bleeding.
Ethanol
Increased plasma ethanol concentration.
HMG-CoA reductase inhibitors (statins)
In patients receiving Staveran, 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 Staveran 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
Enhanced hypotensive effect.
Metformin
Verapamil may reduce the glucose-lowering effect of metformin.

Staveran with food, drink, and alcohol
Interactions may also occur with grapefruit juice and products containing St. John's wort extract.

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor or pharmacist 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, Staveran may affect reaction ability to such an extent that it impairs the ability to drive vehicles and operate machinery or work under hazardous conditions. This is particularly likely during the initial phase of treatment, during dose escalation, when switching from another medicine, 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.

Staveran contains lactose monohydrate
If the patient has previously been diagnosed with intolerance to certain sugars, the patient should consult a doctor before taking this medicine.

Staveran 40 contains lactose with orange-yellow dye (E110), Staveran 80 contains orange-yellow dye (E110), and Staveran 120 contains quinoline yellow (E104)
The medicine may cause allergic reactions.

3. How to use Staveran

This medicine should always be used as directed by your doctor. If in doubt, consult your doctor.

The dosage should 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 in short-term treatment. There is no limitation on the duration of treatment. After prolonged use, the medicine must not be abruptly discontinued. Gradual dose reduction is recommended.

Staveran 40 should be used in patients who are expected to respond adequately to low doses (e.g. patients with liver impairment or elderly patients). For 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 with body weight over 50 kg

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 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 impairment
Caution should be exercised when administering the medicine to patients with renal impairment, and the patient's condition should be closely monitored.

Hepatic impairment
In patients with liver 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 should be exercised when determining dosage in patients with liver impairment, and low doses should be administered during the initial phase of treatment (see section Warnings and precautions).

Method of administration
Oral use. The tablet should be swallowed whole (not sucked or chewed), with sufficient fluid, preferably during or immediately after a meal.

Use of a higher than recommended dose of Staveran
If a higher than recommended dose is taken, seek immediate medical advice or go to the nearest hospital emergency department.

Symptoms of overdose include:
Arterial hypotension, bradycardia, slowed conduction up to high-degree atrioventricular block and sinus node arrest, hyperglycemia, stupor, metabolic acidosis. Fatal outcomes have occurred following overdose.

Treatment
In cases of overdose, supportive treatment should be primarily administered, individually tailored. In cases of intentional oral overdose, β-adrenergic stimulation and/or intravenous calcium (calcium chloride) have been effectively used. In the presence of clinically significant 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 Staveran
Do not take a double dose to make up for a missed dose.

Discontinuation of Staveran
After prolonged use, the medicine must not be abruptly discontinued. Gradual dose reduction is recommended.

If you have any further questions concerning the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
The most commonly observed adverse reactions were: headache, dizziness, gastrointestinal disorders:
nausea, constipation and abdominal pain, as well as bradycardia, tachycardia, palpitations,
arterial hypotension, skin flushing with sensation of warmth, peripheral oedema and fatigue.

Adverse reactions are listed below according to the following frequency classification:
Common (occurring in less than 1 in 10 patients):

• central dizziness, headache,
• bradycardia,
• skin flushing with sensation of warmth, arterial hypotension,
• constipation, nausea,
• peripheral oedema.

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

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

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

• paraesthesia, muscle twitching,
• somnolence,
• tinnitus,
• vomiting, dry mouth,
• excessive sweating.

Adverse reactions occurring at unknown frequency (frequency cannot be estimated from the available data):

• hypersensitivity reactions,
• extrapyramidal disorders, convulsions,
• hyperkalaemia,
• visual disturbances,
• peripheral dizziness,
• atrioventricular block (I°, II°, III°), heart failure, sinus arrest, sinus bradycardia, asystole,
• bronchospasm, dyspnoea, pulmonary oedema,
• abdominal discomfort, gingival hyperplasia, intestinal obstruction,
• angioedema, Stevens-Johnson syndrome, erythema multiforme, alopecia, pruritus, itching, purpura, maculopapular rash, urticaria,
• joint pain, muscle weakness, myalgia,
• renal failure, increased frequency of urination,
• erectile dysfunction, galactorrhoea, gynaecomastia,
• increased prolactin blood concentration, increased liver enzyme activity, occurrence of signs of hepatocyte damage.

Since marketing authorisation, one case of paralysis (quadriparesis) has been reported 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 a doctor, pharmacist or nurse. 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
Adverse reactions can also be reported to the marketing authorisation holder.
Reporting adverse reactions enables better assessment of the benefit-risk balance of the medicine.

5. How to store the medicine Staveran

Keep the medicine out of the 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 stated month.
The marking on the packaging following "EXP" indicates the expiry date, and following "Lot/LOT" indicates the batch number.
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 Staveran contains:

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

What Staveran looks like and contents of the pack
Staveran 40 mg are orange, round, biconvex, film-coated tablets.
Staveran 80 mg are orange, round, biconvex, film-coated tablets with a breakline on one side.
Staveran 120 mg are yellow, round, biconvex, film-coated tablets with a breakline on one side.
Each pack contains 20 or 60 tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Zakłady Farmaceutyczne POLPHARMA S.A.
Pelplinska 19, 83-200 Starogard Gdanski
tel. + 48 22 364 61 01

Manufacturer
Zakłady Farmaceutyczne POLPHARMA S.A.
Medana Branch in Sieradz
Wladyslawa Lokietka 10, 98-200 Sieradz
Zakłady Farmaceutyczne POLPHARMA S.A.
Production Branch in Nowa Dęba
Metalowca 2
39-460 Nowa Dęba