CLIVOTEN 2.5 MG Extended-release hard capsule

Зміст інструкції

1. Clivoten 2.5 mg prolonged-release hard capsules, 5 mg prolonged-release hard capsules
   1. What is Clivoten and what is it used for?
   2. What you need to know before taking Clivoten
   3. How to take Clivoten
   4. Possible side effects
   5. How to store Clivoten
   6. Contents of the pack and other information

Clivoten 2.5 mg prolonged-release hard capsules, 5 mg prolonged-release hard capsules

Isradipine

Read this leaflet carefully before you start taking this medicine because
it contains important information for you

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What is Clivoten and what is it used for?

Clivoten is a hard prolonged-release capsule (the drug is released slowly
over time allowing to prolong the duration of its effect) and contains isradipine, a
substance belonging to a group of medicines called “calcium antagonists”.
Isradipine acts on blood vessels by dilating them and without compromising cardiac
functionality, it causes a lowering of blood pressure when it is too
high (arterial hypertension).
Clivoten is therefore used for the treatment of arterial hypertension.

2. What you need to know before taking Clivoten

Do not take Clivoten

• if you are allergic to medicines containing isradipine or any of the other ingredients of this medicine (listed in section 6);
• if you suffer from unstable angina pectoris (heart disease that causes chest pain even at rest);
• if you suffer from acute myocardial infarction (heart damage due to insufficient blood circulation) or have suffered from it in the previous month;
• if you suffer from aortic stenosis (narrowing or obstruction of the aortic valve of the heart which regulates blood flow between this organ and the rest of the body);
• if you suffer from uncompensated heart failure (insufficient functioning of the heart);
• if you suffer from cardiogenic shock (the heart suddenly fails to pump blood effectively);
• if you are pregnant or breastfeeding.

Do not take Clivoten if any of the conditions listed above apply to you and still talk to your doctor.

Warnings and precautions
Consult your doctor or pharmacist before taking Clivoten.

Pay particular attention with Clivoten:
If you suffer from congestive heart failure (insufficient functioning of the heart that causes fluid accumulation in the tissues), especially if you are also being treated with beta-blocker medicines at the same time.
If you suffer from kidney damage.
If you are hypotensive (suffer from low blood pressure); isradipine may rarely cause hypotension (reduction of blood pressure); in sensitive subjects, it may induce myocardial ischemia (insufficient blood flow to the heart walls).
If you suffer from sick sinus syndrome (a heart disease) confirmed or suspected, and you do not have a pacemaker, as in this case treatment with Clivoten requires particular caution.
If you suffer from severe aortic stenosis (severe narrowing of the aorta), as in this case the use of Clivoten requires extreme caution.
If you suffer from gastrointestinal hypermotility (increased contractions of the stomach and intestines) or gastrointestinal obstruction (closure of a section of the intestine).
If you are using rifampicin (antimicrobial medicine) or with other so-called “enzyme inducers” (medicines that stimulate the metabolism of other medicines reducing their effectiveness), as concomitant administration with Clivoten should be avoided (see “Other medicines and Clivoten”).
If you are undergoing concomitant treatment with anticoagulant medicines (medicines that thin the blood), as concomitant administration with Clivoten requires particular caution (see “Other medicines and Clivoten”).
Taking Clivoten may generate angina pectoris (a heart disease that causes chest pain) predominantly in patients with pre-existing coronary artery disease (blockages of the heart arteries). In these patients, the frequency, duration and severity of angina attacks may increase following rapid increases in Clivoten dosages or at the start of treatment.
In subjects with kidney or liver problems, and in the elderly, the dose should be established based on health conditions. During the first three weeks of treatment, liver function should be carefully monitored.
Persistent skin reactions induced by calcium antagonists may develop, in some cases, up to an exfoliative dermatitis (severe and widespread erythema with skin scaling) or a multiforme erythema (dermatological pathology characterized by one or more target-like lesions on the skin). In these cases, discontinue the use of Clivoten.
If hypersensitivity (allergic) reactions should occur, discontinue the use of Clivoten.

Children
The use of Clivoten capsules in children is not recommended.

Other medicines and Clivoten
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
Clivoten can affect the way some other medicines work. Conversely, some medicines can affect the way Clivoten works.

Avoid the concomitant administration of Clivoten with:

• so-called “enzyme inducers” such as rifampicin(antimicrobial medicine), and antiepileptics such as carbamazepineand phenobarbital, as they significantly reduce the concentrations of isradipine (the active ingredient of Clivoten) in the blood;- phenytoin(a medicine for the treatment of epilepsy and some heart arrhythmias).

Talk to your doctor or pharmacist if you are taking one or more of the following medicines:

• macrolide antibiotics (e.g. erythromycin, clarithromycin, troleandomycin);
• protease enzyme inhibitors, used to control HIV infection (e.g. ritonavir, indinavir, nelfinavir);
• reverse transcriptase inhibitors (an enzyme present in some viruses) (e.g. delavirdine);
• azol antifungal agents (medicines that fight fungal infections) (e.g. ketoconazole, itraconazole, voriconazole);
• antihypertensive medicines(used to lower blood pressure); as with all antihypertensives, concomitant treatment with Clivoten and baclofen (a medicine used for the treatment of muscle spasms) orally (by mouth) may further accentuate a possible drop in blood pressure. It may therefore be necessary to monitor blood pressure and adjust the dosage of the antihypertensive accordingly.
• cimetidine(a medicine used in the treatment of stomach or intestinal ulcers); as concomitant treatment with Clivoten increases the bioavailability (amount of medicine absorbed) of isradipine by about 50% (see “How to take Clivoten”);
• anticoagulants(medicines that thin the blood), as concomitant administration with Clivoten requires particular caution (see “Warnings and precautions”);
• propranolol(a beta-blocker medicine), as isradipine induces a small increase in the bioavailability (amount of medicine absorbed) of propranolol. The clinical relevance of this phenomenon is not known.
• amiodarone(a medicine used in the treatment of some heart arrhythmias); concomitant administration with Clivoten should be avoided if you suffer from

sick sinus syndrome and partial atrioventricular block (two types of heart arrhythmia), as further slowing of the heart rate or worsening of the arrhythmia may occur.
Cases of severe increase in blood pressure have been reported with concomitant use of a beta-blocker and a calcium antagonist (a medicine belonging to the same therapeutic class as Clivoten) during anesthesia with fentanyl (an anesthetic derived from morphine).
The concentration of isradipine (the active ingredient of Clivoten) in the blood increases by about 20% in case of concomitant treatment with diclofenac (a medicine used for the treatment of inflammation), but this is not considered clinically relevant.

Clivoten with drinks and alcohol
Concomitant intake of grapefruit juice may increase the bioavailability (amount of medicine absorbed) of isradipine.
As with all medicines, avoid drinking alcohol while using Clivoten.

Pregnancy, breastfeeding and fertility
Do not take Clivoten during pregnancy or if you are breastfeeding. Do not breastfeed during treatment with Clivoten (see “Do not take Clivoten”).
If you suspect or are planning a pregnancy, ask your doctor or pharmacist for advice before taking this medicine.

Driving and operating machinery
Adverse effects associated with the use of Clivoten, such as syncope (temporary loss of consciousness), dizziness, lowering of blood pressure (hypotension), visual disturbances and blurred vision, may occur.
If you experience these adverse effects, do not drive vehicles or perform tasks that require particular attention.

3. How to take Clivoten

Take this medicine following exactly the instructions of your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.

The recommended dose is:1 prolonged-release hard capsule of 5 mg once a day. The capsules must be swallowed whole.
If after 4 weeks of treatment with a 5 mg capsule once a day the response to therapy is not satisfactory, your doctor may advise you to associate another antihypertensive medicine (preferably a thiazide diuretic, an ACE inhibitor or a beta-blocker).
Clivoten can also be added to pre-existing antihypertensive treatment.
If you are taking cimetidine(a medicine used in the treatment of gastric or duodenal ulcer) at the same time, the dose of Clivoten should be reduced by 50% (see paragraph “Other medicines and Clivoten”).

Use in elderly patients or with liver or kidney problems
If you are elderly or have liver or kidney problems, your doctor may decide to start treatment with a 2.5 mg capsule once a day.
Patients over 65 years of age and patients with liver alterations may present elevated concentrations of isradipine (the active ingredient of Clivoten) in the blood.

If you take more Clivoten than you should
If you take more Clivoten capsules than you should or in case of accidental ingestion of Clivoten, call a doctor or go to the nearest hospital bringing the package of the medicine with you. This way, the doctor will immediately know what you have taken.
Knowledge about the consequences of Clivoten overdose is limited. Available data suggest that overdose may induce a marked and prolonged reduction in blood pressure (hypotension) requiring supportive therapy (to avoid collapse) with monitoring of both cardio-respiratory function and blood volume. Treatment may require the administration of substances with vasoconstrictor activity (which constrict blood vessels), provided their use is not contraindicated. Intravenous calcium infusion may also be used. Consult your doctor in case of Clivoten overdose.

If you forget to take Clivoten
If you have forgotten to take Clivoten, take the dose that has been prescribed to you as soon as you remember. However, if it is almost time to take the next dose, skip the one you have forgotten. Never take a double dose to compensate for the missed dose.

If you stop taking Clivoten
If you have any doubts about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
Many side effects observed during clinical studies of Clivoten were of moderate
severity, generally dose-dependent and related to the vasodilating properties of the
medicine: dizziness, headache, flushing, increased heart rate
(tachycardia), palpitations and peripheral localised edema (swelling). These effects
tend to disappear or regress with continued treatment.

Very common(may affect more than 1 in 10 people)

• headache;
• flushing;
• peripheral edema (swelling).

Common(may affect up to 1 in 10 people)

• dizziness;
• tachycardia (racing heart), palpitations;
• dyspnea (difficulty breathing);
• abdominal discomfort;
• skin rash (change in skin color and texture with red spots or bumps);
• polyuria (production and excretion of large amounts of urine, which appears clear and dilute);
• fatigue, malaise.

Uncommon(may affect up to 1 in 100 people)

• weight gain;
• hypotension (low blood pressure).

Very rare(may affect up to 1 in 10,000 people)

• blood changes: thrombocytopenia (decreased number of platelets), leukopenia (decreased number of white blood cells), anemia (decreased number of red blood cells);
• anorexia, loss of appetite;
• depression, anxiety, nervousness;
• hypoesthesia (decreased sensitivity), paraesthesia (altered sensitivity of limbs or other parts of the body with a sensation of tingling, prickling or itching);
• somnolence;
• impaired vision, blurred vision;
• heart changes: ventricular arrhythmia, myocardial infarction, heart failure, angina pectoris (chest pain due to cardiac cause), atrial fibrillation (an irregular heartbeat), bradycardia (decreased heart rate);
• cough, vomiting, nausea;
• gingival hyperplasia (abnormal growth of the gums);
• abnormal liver function tests, hepatitis (inflammation of the liver);
• allergic dermatitis, allergic skin reactions, itching;
• hyperhidrosis (increased sweating);
• anaphylactic reactions (allergy to the medicine) and angioedema (inflammatory reaction of the skin, characterised by the sudden appearance of swelling of the skin, similar to urticaria);
• photosensitivity (allergy to the sun);
• arthralgia (joint pain), back pain, muscle spasms, pain in the lower limbs;
• pollakiuria (frequent urination of small amounts);
• erectile dysfunction (impotence), gynecomastia (enlargement of the breasts in males);
• asthenia (reduced muscle strength, fatigue, tiredness).

Frequency not known(the frequency cannot be estimated from the available data)

• insomnia;
• transient ischemic attacks (decreased blood supply to the brain);
• syncope (fainting);
• stroke;
• dry mouth;
• constipation, diarrhoea;
• lethargy (continuous sleep);
• chest pain.

The following side effects have been associated with treatment with calcium antagonists:

• exfoliative dermatitis (severe and widespread erythema with skin scaling);
• erythema multiforme (dermatological condition characterised by one or more target-like lesions on the skin).

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any side effects not listed in this leaflet. You can also report side effects directly through the national reporting system at
http://www.agenziafarmaco.gov.it/it/responsabili. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Clivoten

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the pack after
the wording “EXP”. The expiry date refers to the last day of that month.
Do not dispose of any medicine in waste water or household waste. Ask your
pharmacist how to dispose of medicines you no longer use. This will help protect
the environment.

6. Contents of the pack and other information

What Clivoten contains

• The active ingredient is isradipine. Each 5 mg prolonged-release hard capsule contains 5 mg of isradipine; each 2.5 mg prolonged-release hard capsule contains 2.5 mg of isradipine.
• The other excipients are: anhydrous colloidal silica, magnesium stearate, cetyl palmitate, microcrystalline cellulose, hypromellose.
• The capsule components are: yellow iron oxide, titanium dioxide, gelatin.

Description of the appearance of Clivoten and contents of the pack
Clivoten is presented in the form of hard capsules.
The pack of Clivoten 2.5 mg prolonged-release capsules contains 28 capsules.
The pack of Clivoten 5 mg prolonged-release capsules contains 14 capsules.

Marketing Authorisation Holderand manufacturer
ITALFARMACO S.p.A. - Viale Fulvio Testi, 330 – 20126 Milano