Package leaflet: Information for the patient

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

Isradipine
Please read this leaflet carefully before 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 give it to other people, even if their symptoms are the same as yours, as it may be harmful.
If you experience any side effects, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

What Clivoten is and what it is used for
What you need to know before taking Clivoten
How to take Clivoten
Possible side effects
How to store Clivoten
Contents of the pack and other information

1. What Clivoten is and what it is used for

Clivoten is a hard prolonged-release capsule (the drug is released slowly over time, allowing its effect to last longer) and contains isradipine, a substance belonging to a group of medicines called "calcium antagonists".
Isradipine acts on blood vessels by dilating them, thereby lowering blood pressure when it is too high (arterial hypertension), without compromising cardiac function.
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 (a heart condition causing chest pain even at rest);
if you have acute myocardial infarction (heart damage due to inadequate blood flow) or have had one in the previous month;
if you suffer from aortic stenosis (narrowing or obstruction of the aortic valve of the heart regulating blood flow between the heart and the rest of the body);
if you suffer from uncompensated heart failure (inadequate heart function);
if you suffer from cardiogenic shock (sudden inability of the heart to pump blood effectively);
if you are pregnant or breastfeeding.

Do not take Clivoten if any of the above conditions apply to you, and discuss this with your doctor.
Warnings and precautions
Talk to your doctor or pharmacist before taking Clivoten.
Exercise special caution with Clivoten :
If you suffer from congestive heart failure (inadequate heart function causing fluid accumulation in tissues), especially if you are simultaneously being treated with beta-blocking agents.
If you have kidney impairment.
If you are hypotensive (have low blood pressure); isradipine may rarely cause hypotension (reduction in blood pressure); in sensitive individuals, it may induce myocardial ischemia (inadequate blood flow to the heart walls).
If you have confirmed or suspected sinoatrial node syndrome (a heart condition) and do not have a pacemaker, as treatment with Clivoten requires particular caution in such cases.
If you suffer from severe aortic stenosis (significant narrowing of the aorta), as use of Clivoten requires extreme caution in this case.
If you suffer from gastrointestinal hypermotility (increased contractions of the stomach and intestines) or gastrointestinal obstruction (blockage in a section of the intestine).
If you are taking rifampicin (an antimicrobial medicine) or other so-called "enzyme-inducing" medicines (medicines that stimulate the metabolism of other drugs, reducing their effectiveness), as concomitant administration with Clivoten must be avoided (see "Other medicines and Clivoten").
If you are concurrently being treated with anticoagulant medicines (medicines that thin the blood), as concomitant administration with Clivoten requires particular caution (see "Other medicines and Clivoten").
The intake of Clivoten may trigger angina pectoris (a heart condition causing chest pain), particularly in patients with pre-existing coronary artery disease (obstruction of the heart arteries). In these patients, the frequency, duration, and severity of angina attacks may increase following rapid dose escalation or at the beginning of treatment.
In patients with kidney or liver problems, and in elderly patients, the dose should be adjusted according to health status. Liver function should be closely monitored during the first three weeks of treatment.
Persistent skin reactions induced by calcium antagonists may occur, in some cases progressing to exfoliative dermatitis (severe widespread erythema with skin peeling) or erythema multiforme (a dermatological condition characterized by one or more target-like skin lesions). In such cases, discontinue use of Clivoten.
If hypersensitivity reactions (allergic reactions) occur, discontinue use of Clivoten.
Children
The use of Clivoten capsules in children is not recommended.
Other medicines and Clivoten
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicine.
Clivoten may affect how certain other medicines work. Conversely, some medicines may affect how Clivoten works.
Avoid concomitant administration of Clivoten with:

medicines known as "enzyme inducers" such as rifampicin (an antimicrobial medicine), and antiepileptics such as carbamazepine and phenobarbital, as they significantly reduce blood concentrations of isradipine (the active substance in Clivoten);

phenytoin (a medicine used to treat epilepsy and certain cardiac 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 inhibitors used to control HIV infection (e.g. ritonavir, indinavir, nelfinavir);
reverse transcriptase inhibitors (an enzyme present in certain viruses) (e.g. delavirdine);
azole antifungal medicines (medicines that treat fungal infections) (e.g. ketoconazole, itraconazole, voriconazole);
antihypertensive medicines (used to lower blood pressure); as with all antihypertensives, concomitant treatment with Clivoten and oral baclofen (a medicine used to treat muscle spasms) may further accentuate a potential drop in blood pressure. Monitoring of blood pressure and adjustment of antihypertensive dosage may therefore be necessary;
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 approximately 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-blocking agent), as isradipine induces a slight increase in the bioavailability (amount of medicine absorbed) of propranolol. The clinical relevance of this effect is unknown.
amiodarone (a medicine used to treat certain cardiac arrhythmias); concomitant administration with Clivoten should be avoided if you suffer from

sinoatrial node syndrome and partial atrioventricular block (two types of cardiac arrhythmia), as it may lead to further slowing of heart rate or worsening of the arrhythmia.
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 (a morphine-derived anesthetic).
Blood concentrations of isradipine (the active substance in Clivoten) increase by approximately 20% with concomitant treatment with diclofenac (a medicine used to treat inflammation), but this is not considered clinically significant.
Clivoten with food and alcohol
Concomitant intake of grapefruit juice may increase the bioavailability (amount of medicine absorbed) of isradipine.
As with all medicines, avoid alcohol consumption while taking Clivoten.
Pregnancy, breastfeeding and fertility
Do not take Clivoten during pregnancy or while breastfeeding. During treatment with Clivoten, you must not breastfeed (see "Do not take Clivoten").
If you suspect you are pregnant or are planning a pregnancy, consult your doctor or pharmacist before taking this medicine.
Driving and using machines
Adverse effects associated with the use of Clivoten may occur, such as syncope (transient loss of consciousness), dizziness, low blood pressure (hypotension), visual disturbances, and blurred vision.
If you experience such adverse effects, you must not drive or perform tasks requiring special alertness.

3. How to take Clivoten

Take this medicine exactly as directed by your doctor or pharmacist. If you are unsure, consult your doctor or pharmacist.
The recommended dose is: 1 prolonged-release hard capsule containing 5 mg once daily. The capsules must be swallowed whole.
If after 4 weeks of treatment with one 5 mg capsule once daily the therapeutic response is not satisfactory, your doctor may advise adding another antihypertensive medicine (preferably a thiazide diuretic, an ACE inhibitor or a beta-blocker).
Clivoten may also be added to an 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 section “Other medicines and Clivoten”).

Use in elderly patients or in patients with liver or kidney problems
If you are elderly or have liver or kidney problems, your doctor may decide to start treatment with one 2.5 mg capsule once daily.
Patients over 65 years of age and patients with liver impairment may have increased blood concentrations of isradipine (the active substance in Clivoten).

If you take more Clivoten than you should
If you take more Clivoten capsules than prescribed or if Clivoten is accidentally ingested, call a doctor or go to the nearest hospital, taking the medicine pack with you. This way, the doctor will immediately know what you have taken.
Experience regarding the consequences of Clivoten overdose is limited. Available data suggest that overdose may cause a marked and prolonged reduction in blood pressure (hypotension), requiring supportive therapy (to prevent collapse), with monitoring of cardio-respiratory function and blood volume. Treatment may include administration of vasoconstrictive agents (which narrow 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 forget to take Clivoten, take the prescribed dose as soon as you remember. However, if it is almost time for your next dose, skip the missed dose. Never take a double dose to make up for a forgotten dose.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Many of the side effects observed in clinical studies with Clivoten are of moderate severity, generally dose-dependent and related to the vasodilatory properties of the medicine: dizziness, headache, flushing, increased heart rate (tachycardia), palpitations, and peripheral oedema (swelling). These effects tend to disappear or diminish with continued treatment.

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

headache;
flushing;
peripheral oedema (swelling).

Common (may affect up to 1 in 10 people)

dizziness;
tachycardia (rapid heartbeat), palpitations;
dyspnoea (difficulty breathing);
abdominal discomfort;
rash (change in skin colour and texture, with red spots or bumps appearing);
polyuria (production and excretion of large amounts of urine, which appear clear and diluted);
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 disorders: thrombocytopenia (decreased number of platelets), leucopenia (decreased number of white blood cells), anaemia (decreased number of red blood cells);
anorexia, loss of appetite;
depression, anxiety, nervousness;
hypoesthesia (reduced sensitivity), paraesthesia (altered sensation in limbs or other body parts, with tingling, prickling or itching);
somnolence;
visual disturbances, blurred vision;
heart disorders: ventricular arrhythmia, myocardial infarction, heart failure, angina pectoris (chest pain of cardiac origin), atrial fibrillation (a disturbance in heart rhythm), bradycardia (reduced heart rate);
cough, vomiting, nausea;
gingival hyperplasia (abnormal overgrowth of the gums);
liver function test abnormalities, hepatitis (liver inflammation);
allergic dermatitis, allergic skin reactions, pruritus;
hyperhidrosis (increased sweating);
anaphylactic reactions (allergic reaction to the medicine) and angioedema (inflammatory skin reaction characterised by sudden onset of swelling of the skin, similar to urticaria);
photosensitivity (allergy to sunlight);
arthralgia (joint pain), back pain, muscle spasms, pain in lower limbs;
pollakiuria (frequent urination of small volumes);
erectile dysfunction (impotence), gynaecomastia (enlargement of breast tissue in males);
asthenia (reduced muscle strength, fatigue, weakness).

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

insomnia;
transient ischaemic attacks (temporary reduction in blood supply to the brain);
syncope (fainting);
stroke;
dry mouth;
constipation, diarrhoea;
lethargy (prolonged drowsiness);
chest pain.

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

exfoliative dermatitis (severe, widespread erythema with skin peeling);
erythema multiforme (a skin condition characterised by one or more target-shaped lesions on the skin, resembling a bullseye).

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. You may also report side effects directly via 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 stated on the carton after the wording “EXP”. The expiry date refers to the last day of that month.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Clivoten contains

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

Description of the appearance of Clivoten and package contents
Clivoten is available as 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 Authorization Holder and Manufacturer
ITALFARMACO S.p.A. - Viale Fulvio Testi, 330 – 20126 Milan, Italy