Lopridam

Patient information leaflet

Lopridam 4 mg/1.25 mg/5 mg tablets, 4 mg/1.25 mg/10 mg tablets, 8 mg/2.5 mg/5 mg tablets, 8 mg/2.5 mg/10 mg tablets

Perindopril erbumine/indapamide/amlodipine
Please read all of 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 they have the same symptoms as yours, because it could 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:

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

1. What Lopridam is and what it is used for

Lopridam is a combination of three active substances: perindopril, indapamide and amlodipine. It is an antihypertensive medicine used to treat high blood pressure (hypertension).
Lopridam is used to treat high blood pressure in patients whose blood pressure is already controlled with the combination of perindopril/indapamide and amlodipine, taken at the same dosage.
Each active substance reduces blood pressure, and together they act to control your blood pressure:
Perindopril belongs to a class of medicines called ACE inhibitors. These medicines work by dilating blood vessels; this makes it easier for your heart to pump blood through them.
Indapamide is a diuretic. Diuretics increase the amount of urine produced by the kidneys. However, indapamide differs from other diuretics in that it causes only a slight increase in the amount of urine produced.
Amlodipine belongs to a class of medicines called calcium antagonists. In patients with high blood pressure, this medicine works by relaxing blood vessels, making it easier for blood to flow through them.

2. What you need to know before taking Lopridam

Do not take Lopridam

• if you are allergic to perindopril or any other ACE inhibitor, to indapamide, to any other sulfonamide, to amlodipine or other calcium antagonists, or to any of the other ingredients of this medicine (listed in section 6).
• if you have previously experienced symptoms such as shortness of breath, facial or tongue swelling, intense itching, or severe skin rashes related to prior treatment with an ACE inhibitor, or if you have ever had such symptoms under any circumstances (a condition called angioedema).
• if you have taken or are currently taking sacubitril/valsartan, a medicine used to treat chronic heart failure in adults, as this increases the risk of angioedema (rapid swelling beneath the skin, for example in the throat).
• if you have diabetes or impaired kidney function and are being treated with a blood pressure-lowering medicine containing aliskiren.
• if you have severe liver disease or a condition called hepatic encephalopathy (a degenerative brain disorder).
• if you have severe kidney disease with significantly reduced blood flow to the kidneys (renal artery stenosis).
• if you are undergoing dialysis or any other type of blood filtration. Depending on the machine used, Lopridam may not be suitable for you.
• if you have low or high levels of potassium in your blood.
• if you suspect you have untreated decompensated heart failure (severe fluid retention, breathing difficulties).
• if you have narrowing of the aortic heart valve (aortic stenosis) or cardiogenic shock (a condition in which your heart cannot supply enough blood to the body).
• if you have heart failure following a heart attack.
• if you suffer from severely low blood pressure (hypotension).
• if you are more than three months pregnant (Lopridam should also be avoided during early pregnancy – see “Pregnancy and breastfeeding”).

Warnings and precautions
Talk to your doctor or pharmacist before taking Lopridam.
You must inform your doctor if you have or have had any of the following conditions:

• aortic stenosis (narrowing of the main blood vessel leaving the heart), hypertrophic cardiomyopathy (a heart muscle disease), or renal artery stenosis (narrowing of the artery supplying blood to the kidneys).
• recent heart attack.
• heart failure or any other heart condition.
• kidney problems or if you are on dialysis.
• abnormally high levels of a hormone called aldosterone in your blood (primary hyperaldosteronism).
• severe increase in blood pressure (hypertensive crisis).
• liver disease.
• a collagen disease (skin disease) such as systemic lupus erythematosus or scleroderma.
• atherosclerosis (hardening of the arteries).
• hyperparathyroidism (overactive parathyroid gland).
• gout.
• diabetes.
• if you are on a low-salt diet or use potassium-containing salt substitutes.
• if you suffer from muscle disorders including muscle pain, tenderness, weakness, or cramps.
• if you are taking lithium or potassium-sparing drugs (spironolactone, triamterene) or potassium supplements, as their use with Lopridam should be avoided.
• if you are elderly and your dosage needs to be increased.
• if you experience vision disturbances or eye pain. These could be symptoms of fluid accumulation in the vascular layer of the eye (choroidal effusion) or increased eye pressure and may occur from a few hours to weeks after taking Lopridam. This condition may lead to permanent vision loss if not treated. If you previously had an allergy to penicillin or sulfonamides, you may be at higher risk.
• if you have experienced photosensitivity reactions.
• if you have had a severe allergic reaction with rapid swelling beneath the skin in areas such as the face, lips, mouth, tongue, or throat, which may cause difficulty swallowing or breathing (angioedema). This may occur at any time during treatment. If you develop such symptoms, you must stop treatment immediately and consult a doctor without delay. See also section 4.
• if you are taking any of the following medicines, as they may increase the risk of angioedema:
• racecadotril, a medicine used to treat diarrhoea.
• medicines used to prevent rejection of transplanted organs and to treat cancer (such as temsirolimus, sirolimus, everolimus, and other medicines belonging to the class of mTOR inhibitors).
• vildagliptin, a medicine used to treat diabetes.
• if you are of Black ethnicity, as you may have a higher incidence of angioedema and this medicine may be less effective in lowering your blood pressure compared to non-Black patients.
• if you are a dialysis patient undergoing haemodialysis with high-flux membranes.
• if you are taking any of the following medicines for high blood pressure:
• an angiotensin II receptor blocker (ARB) (also known as sartans – e.g. valsartan, telmisartan, irbesartan), particularly if you have kidney problems related to diabetes.
• aliskiren. Your doctor may monitor your kidney function, blood pressure, and electrolyte levels (e.g. potassium) at regular intervals.

See also the section "Do not take Lopridam".
You must inform your doctor if you think you are pregnant (or if there is a possibility of becoming pregnant). Lopridam is not recommended during early pregnancy and must not be taken if you are more than three months pregnant, as it may cause severe harm to the unborn child if taken during this period (see section “Pregnancy and breastfeeding”).
If you are taking Lopridam, inform your doctor or medical staff:

• if you are due to undergo anaesthesia and/or surgery.
• if you have recently had diarrhoea or vomiting, or if you are dehydrated.
• if you are due to undergo dialysis or LDL apheresis (blood purification to remove cholesterol using a machine).
• if you are undergoing desensitisation treatment to reduce allergic reactions to bee or wasp stings.
• if you are scheduled for a medical examination requiring injection of an iodinated contrast agent (a substance used to make organs such as kidneys or stomach visible on X-rays).

Athletes should be aware that Lopridam contains an active substance (indapamide) that may lead to a positive result in doping tests.
Children and adolescents
Lopridam must not be administered to children or adolescents.
Other medicines and Lopridam
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
You must not take Lopridam with:

• lithium (used to treat mania or depression).
• aliskiren (a medicine used to treat hypertension) if you have diabetes mellitus or kidney problems.
• potassium supplements (including salt substitutes), potassium-sparing diuretics, and other medicines that may increase potassium levels in the blood (such as trimethoprim and cotrimoxazole for treating bacterial infections; cyclosporine, an immunosuppressant used to prevent transplant rejection; and heparin, a medicine used to thin the blood and prevent clotting).
• estramustine (used in cancer therapy).
• other medicines used to treat high blood pressure: angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers.
• sacubitril/valsartan – used to treat chronic heart failure in adults (see also information under “Do not take Lopridam”).

Treatment with Lopridam may affect or be affected by other medicines. Make sure to inform your doctor if you are taking any of the following medicines. Your doctor may consider it necessary to adjust your dose and/or take other precautions:

• other medicines for treating high blood pressure, including an angiotensin II receptor blocker (ARB) or aliskiren (see also information under “Do not take Lopridam” and “Warnings and precautions”),
• potassium-sparing diuretics used in heart failure treatment: eplerenone and spironolactone at doses between 12.5 mg and 50 mg daily,
• anaesthetics,
• iodinated contrast agents,
• moxifloxacin, sparfloxacin (antibiotics: medicines used to treat infections),
• methadone (used to treat addiction),
• procainamide (for treating irregular heartbeat),
• allopurinol (for treating gout),
• mizolastine, terfenadine or astemizole (antihistamines for hay fever or allergies),
• corticosteroids used to treat various conditions including severe asthma and rheumatoid arthritis,
• immunosuppressants such as tacrolimus (used to control the body’s immune response, allowing acceptance of transplanted organs),
• intravenous gold salts (used to treat rheumatoid polyarthritis),
• cancer treatment medicines,
• halofantrine (used to treat certain types of malaria),
• pentamidine (used to treat pneumonia),
• intravenous gold salts (used to treat rheumatoid arthritis),
• vincamine (used to treat symptomatic cognitive disorders in the elderly, including memory loss),
• bepridil (used to treat angina pectoris),
• sultopride (for treating psychosis),
• medicines used for heart rhythm disorders (e.g. quinidine, hydroquinidine, disopyramide, amiodarone, sotalol),
• cisapride, difemanil (used to treat gastrointestinal and digestive problems),
• digoxin and other cardiac glycosides (for treating heart conditions),
• baclofen (used to treat muscle stiffness in conditions such as multiple sclerosis),
• medicines for treating diabetes such as insulin, metformin or gliptins (such as vildagliptin),
• calcium, including calcium supplements,
• stimulant laxatives (e.g. senna),
• non-steroidal anti-inflammatory drugs (e.g. ibuprofen) or high-dose salicylates (e.g. aspirin),
• intravenous amphotericin B (for treating serious fungal diseases),
• medicines for treating mental health disorders such as depression, anxiety, schizophrenia (e.g. tricyclic antidepressants, neuroleptics),
• tetracosactide (for treating Crohn’s disease),
• medicines more commonly used to treat diarrhoea (racecadotril) or prevent rejection of transplanted organs (sirolimus, everolimus, temsirolimus and other medicines belonging to the so-called mTOR inhibitors class). See section “Warnings and precautions”,
• medicines used to treat low blood pressure, shock, or asthma (e.g. ephedrine, noradrenaline or adrenaline),
• ketoconazole, itraconazole (antifungal medicines),
• ritonavir, indinavir, nelfinavir (so-called protease inhibitors used to treat HIV),
• rifampicin, erythromycin, clarithromycin (antibiotics: for treating bacterial infections),
• Hypericum perforatum (St. John’s wort),
• verapamil, diltiazem (heart medicines),
• dantrolene (infusion for severe body temperature abnormalities),
• simvastatin (a medicine to lower cholesterol).

Lopridam with food and drinks
People taking Lopridam must not consume grapefruit or grapefruit juice. This is because grapefruit and its juice may increase blood levels of the active ingredient amlodipine, leading to an unpredictable increase in the blood pressure-lowering effect of Lopridam.
Pregnancy and breastfeeding
If you are pregnant, think you might be pregnant, planning a pregnancy, or breastfeeding, consult your doctor or pharmacist before using this medicine.
Pregnancy
You must inform your doctor if you think you are pregnant (or if there is a possibility of becoming pregnant). Your doctor will usually advise you to stop taking Lopridam before starting a pregnancy or as soon as you know you are pregnant, and will recommend an alternative medicine.
Lopridam is not recommended during early pregnancy and must not be taken after the first three months of pregnancy, as it may cause serious harm to your unborn child if taken beyond the third month of pregnancy.
Breastfeeding
Lopridam is not recommended if you are breastfeeding.
Inform your doctor if you are breastfeeding or planning to breastfeed.
Contact your doctor immediately.
Driving and using machines
Lopridam may affect your ability to drive or operate machinery. If the tablets make you feel unwell, dizzy, tired, or cause headaches, avoid driving or operating machinery and contact your doctor immediately.
Lopridam contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per tablet, i.e. essentially "sodium-free".

3. How to take Lopridam

Use this medicine exactly as directed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
The recommended dose is one tablet per day.
Your doctor may decide to adjust the dosage regimen if you have renal impairment.
Take your tablet with a glass of water, preferably in the morning and before a meal.

If you take more Lopridam than you should
If you take too many tablets, contact the nearest hospital emergency department or inform your doctor immediately. Taking too many tablets may cause a drop in your blood pressure, which could become dangerously low. You may experience dizziness, lightheadedness, fainting, or weakness. If the drop in blood pressure is severe enough, shock may occur. Your skin may become cold and clammy, and you may lose consciousness.
Excess fluid may accumulate in the lungs (pulmonary edema), causing shortness of breath, which may develop up to 24–48 hours after ingestion.
If you have taken an excessive number of Lopridam tablets, contact your doctor immediately.

If you forget to take Lopridam
It is important that you take the medicine every day, as regular treatment is more effective.
However, if you forget to take a dose of Lopridam, take the next dose as usual. Do not take a double dose to make up for the missed dose.

If you stop taking Lopridam
Since treatment with Lopridam for high blood pressure is usually lifelong, you must speak to your doctor before stopping this medicine. Your condition may return if you stop using this medicine before advised to do so.

If you have any questions about how to use this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.

Stop taking the medicine and consult a doctor immediately if you experience any of the following side effects, which may be serious:

• sudden wheezing, chest pain, shortness of breath or difficulty breathing (uncommon) (may affect up to 1 in 100 people),
• swelling of the eyelids, face, lips, mouth, tongue or throat causing severe difficulty in breathing (angioedema) (see section 2 "Warnings and precautions") (uncommon) (may affect up to 1 in 100 people),
• severe dizziness or fainting due to low blood pressure (common) (may affect up to 1 in 10 people),
• cardiovascular disorders – irregular heartbeat, angina pectoris (chest, jaw and back pain triggered by physical exertion), heart attack (very rare) (may affect up to 1 in 10,000 people),
• abnormally fast or irregular heartbeat that may be life-threatening (torsades de pointes) (frequency not known) (frequency cannot be estimated from the available data),
• severe skin reactions including rashes that often start with itchy red patches on the face, arms or legs (erythema multiforme), severe reddening of the skin, hives, widespread skin redness, intense itching, blisters, skin peeling and swelling, inflammation of mucous membranes (Stevens-Johnson syndrome, toxic epidermal necrolysis) or other allergic reactions (very rare) (may affect up to 1 in 10,000 people),
• weakness of the arms or legs, or speech difficulties which could be signs of a possible stroke (very rare) (may affect up to 1 in 10,000 people),
• inflammation of the pancreas which may cause severe abdominal and back pain accompanied by a strong feeling of illness (very rare) (may affect up to 1 in 10,000 people),
• yellowing of the skin or eyes (jaundice), which could be a sign of hepatitis (very rare) (may affect up to 1 in 10,000 people),
• brain disease caused by liver disease (hepatic encephalopathy) (frequency not known) (frequency cannot be estimated from the available data),
• muscle weakness, cramps, tenderness or pain, particularly if associated with feeling unwell or having a high temperature, which may be due to abnormal muscle breakdown (rhabdomyolysis) (frequency not known).

Other possible side effects:
Since Lopridam is a combination of three active substances, the side effects reported are related to the use of the combination perindopril/indapamide or to the use of amlodipine.

Side effects related to the use of perindopril/indapamide

Common (may affect up to 1 in 10 people):

• skin reactions in individuals predisposed to allergic and asthmatic reactions,
• headache,
• dizziness,
• vertigo,
• tingling,
• visual disturbances,
• ringing in the ears (tinnitus),
• cough, shortness of breath (dyspnoea),
• feeling unwell (nausea), vomiting, abdominal pain, taste disturbances, indigestion or digestive difficulties, diarrhoea, constipation,
• skin reactions such as rashes, itching,
• low potassium levels in the blood,
• muscle cramps,
• feeling of weakness.

Uncommon (may affect up to 1 in 100 people):

• mood changes,
• sleep disturbances,
• depression,
• hives,
• red spots on the skin (purpura),
• clusters of blisters on the skin,
• kidney problems,
• impotence (inability to achieve or maintain erection),
• sweating,
• elevated eosinophil count (a type of white blood cells),
• changes in laboratory parameters: elevated potassium levels in the blood (reversible upon discontinuation of treatment), low sodium levels in the blood which may lead to dehydration and low blood pressure,
• drowsiness,
• fainting,
• awareness of your heartbeat (palpitations),
• rapid heartbeat (tachycardia),
• very low blood sugar levels (hypoglycaemia) in diabetic patients,
• inflammation of blood vessels (vasculitis),
• dry mouth,
• increased sensitivity of the skin to sunlight (photosensitivity reactions),
• joint pain (arthralgia),
• muscle pain (myalgia),
• chest pain,
• malaise,
• peripheral oedema,
• fever,
• increased plasma urea, increased plasma creatinine,
• falls.

Rare (may affect up to 1 in 1,000 people):

• dark-coloured urine, feeling unwell (nausea) or unwell state (vomiting), muscle cramps, confusion and seizures. These symptoms may be related to a condition called SIADH (syndrome of inappropriate antidiuretic hormone secretion),
• flushing,
• worsening of psoriasis,
• reduced or absent urine output,
• acute renal failure,
• changes in laboratory parameters: increased liver enzymes, high serum bilirubin levels,
• low chloride levels in the blood,
• low magnesium levels in the blood,
• fatigue.

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

• decreased platelet count in the blood, which may lead to unusual bruising or tendency to bleed,
• decreased white blood cell count,
• decreased red blood cell count (anaemia),
• low haemoglobin levels in the blood,
• high calcium levels in the blood,
• abnormal liver function,
• confusion,
• eosinophilic pneumonia (a rare type of pneumonia),
• blocked or runny nose (rhinitis).

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

• abnormal ECG (electrocardiogram) findings,
• changes in laboratory parameters: elevated uric acid and blood sugar levels,
• muscle weakness,
• myopia, blurred vision,
• decreased vision and/or eye pain due to increased pressure (possible signs of fluid accumulation in the vascular layer of the eye (choroidal effusion) or acute angle-closure glaucoma),
• if you suffer from systemic lupus erythematosus (a collagen disease), this may worsen,
• abnormal colour, numbness and pain in fingers or toes (Raynaud's phenomenon).

Blood, kidney, liver or pancreas disorders and abnormal laboratory parameters (blood test results) may occur. Your doctor may decide to perform blood tests to monitor your health status.

Side effects related to the use of amlodipine

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

• fluid retention (oedema).

Common (may affect up to 1 in 10 people):

• shortness of breath,
• headache, dizziness, drowsiness (especially at the beginning of treatment),
• awareness of your heartbeat (palpitations), hot flushes,
• abdominal pain, feeling unwell (nausea),
• changes in bowel habits, diarrhoea, constipation, indigestion,
• fatigue, feeling of weakness,
• visual disturbances, double vision,
• muscle cramps,
• swollen ankles.

Uncommon (may affect up to 1 in 100 people):

• mood changes, anxiety, depression, insomnia,
• tremors, taste disturbances, fainting,
• sensation of noise or ringing in the ears (tinnitus),
• irregular heartbeat,
• blocked or runny nose (rhinitis),
• cough,
• dry mouth, feeling sick (vomiting),
• hair loss, increased sweating, itching, rash, red spots on the skin (purpura), skin discoloration, hives,
• difficulty urinating, increased need to urinate at night, increased frequency of urination,
• inability to achieve an erection, discomfort or breast enlargement in men,
• pain, feeling unwell,
• joint or muscle pain, back pain, chest pain,
• weight gain or weight loss.

Rare (may affect up to 1 in 1,000 people):

• confusion.

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

• decreased white blood cell count,
• decreased platelet count in the blood, which may cause unusual bruising or easy bleeding,
• high blood sugar levels (hyperglycaemia),
• nerve disorders which may cause muscle weakness, tingling or numbness,
• swollen gums,
• abdominal swelling (gastritis),
• liver inflammation (hepatitis), yellowing of the skin (jaundice), increased liver enzyme levels,
• increased muscle tension,
• a skin rash that often starts with itchy red spots on the face, arms and legs (erythema multiforme),
• inflammation of blood vessels, often with skin rashes,
• changes in skin appearance after exposure to sunlight or artificial UVA (photosensitivity reaction).

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

• tremors, postural rigidity, mask-like face, slow movements and unsteady, shuffling gait.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni.avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Lopridam

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and blister after "EXP".
The expiry date refers to the last day of that month.
This medicine does not require any special storage temperature.
Store in the original blister to protect the medicine from light and moisture.
Do not dispose of this medicine via wastewater 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 Lopridam Contains
The active substances are perindopril erbumine, indapamide and amlodipine besilate.
Lopridam 4 mg/1.25 mg/5 mg tablets
Each tablet contains 4 mg of perindopril erbumine equivalent to 3.338 mg of perindopril, 1.25 mg of
indapamide and 5 mg of amlodipine as amlodipine besilate.
Lopridam 4 mg/1.25 mg/10 mg tablets
Each tablet contains 4 mg of perindopril erbumine equivalent to 3.338 mg of perindopril, 1.25 mg of
indapamide and 10 mg of amlodipine as amlodipine besilate.
Lopridam 8 mg/2.5 mg/5 mg tablets
Each tablet contains 8 mg of perindopril erbumine equivalent to 6.676 mg of perindopril, 2.5 mg of
indapamide and 5 mg of amlodipine as amlodipine besilate.
Lopridam 8 mg/2.5 mg/10 mg tablets
Each tablet contains 8 mg of perindopril erbumine equivalent to 6.676 mg of perindopril, 2.5 mg of
indapamide and 10 mg of amlodipine as amlodipine besilate.

The other components are:
microcrystalline cellulose PH-112, anhydrous calcium hydrogen phosphate; red iron oxide (E172); sodium croscarmellose; anhydrous colloidal silica; magnesium stearate.

Description of the Appearance of Lopridam and Contents of the Pack
Lopridam 4 mg/1.25 mg/5 mg tablets: round, dark pink marbled tablets, 7 mm in diameter, with "4 1.25 5" engraved on one side.
Lopridam 4 mg/1.25 mg/10 mg tablets: round, light pink tablets, 9.4 mm in diameter, with "4 1.25 10" engraved on one side.
Lopridam 8 mg/2.5 mg/5 mg tablets: round, pink marbled tablets, 9.4 mm in diameter, with "8 2.5 5" engraved on one side.
Lopridam 8 mg/2.5 mg/10 mg tablets: round, dark pink marbled tablets, 9.4 mm in diameter, with "8 2.5 10" engraved on one side.

Lopridam is available in OPA/Alu/PVC/Alu blisters.
Pack sizes: 30, 60, 90 tablets.
Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer
Zentiva Italia S.r.l. Via P. Paleocapa 7, 20121 Milano, Italy

Manufacturer
Zentiva, k.s.
U kabelovny 130
102 37 Prague 10 – Dolní Měcholupy
Czech Republic

This medicinal product is authorized in the European Economic Area countries under the following names:
Bulgaria: Приндал
Czech Republic: Lopridam
Italy: Lopridam
Slovak Republic: Lopridam