Rimal

Package leaflet: Information for the patient

Rimal, 5 mg + 5 mg, hard capsules
Rimal, 5 mg + 10 mg, hard capsules
Rimal, 10 mg + 5 mg, hard capsules
Rimal, 10 mg + 10 mg, hard capsules
Ramiprilum + Amlodipinum
Please read this leaflet carefully before taking this medicine, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please ask your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm someone else, even if their symptoms are the same.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Table of contents

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

1. What Rimal is and what it is used for

Rimal contains two active substances – ramipril and amlodipine. Ramipril belongs to a group of medicines called ACE inhibitors (angiotensin-converting enzyme inhibitors), while amlodipine belongs to a group of medicines called calcium antagonists.
Ramipril works by:

• reducing the body's production of substances that may increase blood pressure,
• relaxing and widening blood vessels,
• helping the heart to pump blood throughout the body. Amlodipine works by:
• relaxing and widening blood vessels.

Rimal may be used in the treatment of high blood pressure (hypertension) in adult patients whose blood pressure is adequately controlled when both active substances are taken simultaneously in the same doses as in Rimal, but in separate preparations.

2. Important information before taking Rimal

When not to take Rimal

• if you are allergic to ramipril, amlodipine (the active substances), other medicines from the dihydropyridine calcium antagonist group, other ACE inhibitors, or to any of the other ingredients of this medicine (listed in section 6). Symptoms of an allergic reaction may include: itching, rash, difficulty swallowing or breathing, and swelling of lips, face, throat, or tongue;
• if you have liver function disorders;
• if you have unstable heart failure following an acute myocardial infarction;
• if you have shock, including cardiogenic shock (due to acute heart failure);
• if you have obstruction of the outflow from the left ventricle (e.g. significant aortic valve stenosis);
• if you have ever experienced a severe allergic reaction called angioedema. Symptoms include: itching, urticaria, red spots on hands, feet, and throat, swelling of the throat and tongue, swelling around eyes and lips, difficulty breathing and swallowing;
• if you are undergoing dialysis or other type of blood filtration. Depending on the equipment used, treatment with Rimal may not be suitable;
• if you have a kidney disease causing reduced blood flow to the kidney (renal artery stenosis);
• after the 3rd month of pregnancy (see section "Pregnancy and breastfeeding");
• if you have abnormally low or unstable blood pressure – your doctor will recommend appropriate monitoring;
• if you have diabetes or kidney function disorders and are being treated with a blood pressure-lowering medicine containing aliskiren;
• if you are taking or have taken a combination medicine containing sacubitril and valsartan (used in the treatment of chronic heart failure in adults), as this increases the risk of angioedema (rapid swelling of subcutaneous tissue, e.g. in the throat area).

Do not take Rimal if any of the above conditions apply to you.
If in doubt, speak to your doctor before taking Rimal.

Warnings and precautions

Before starting to take Rimal, discuss this with your doctor or pharmacist. Inform your doctor if any of the following apply to you:

• if you are elderly;
• if you have heart or kidney disorders;
• if you experience sudden swelling of the face, lips, tongue, and (or) throat, and difficulty breathing or swallowing. These may be symptoms of angioedema (a severe allergic reaction) – if this occurs, stop taking Rimal immediately and contact your doctor;
• if you are at risk of impaired blood circulation to the heart or brain due to very low blood pressure;
• if you have experienced significant loss of electrolytes or fluids from the body (due to vomiting, diarrhoea, excessive sweating, low-sodium diet, prolonged use of diuretics (water tablets), or dialysis);
• if you are undergoing treatment to reduce allergic reactions to bee or wasp venom (desensitization therapy);
• if you are scheduled for anaesthetics, either for surgery or dental procedures. You may need to stop taking Rimal one day before – your doctor will advise you accordingly;
• if you have high potassium levels in the blood (detected in a blood laboratory test);
• if you have collagenosis (connective tissue disease), e.g. scleroderma or systemic lupus erythematosus;
• if you are of black race – such patients have an increased risk of angioedema, and the effect of medicines in the class to which ramipril belongs may be reduced (insufficient blood pressure reduction);
• if you develop a persistent dry cough;
• if you are taking any of the following medicines used to treat high blood pressure:
  • an angiotensin II receptor antagonist (AIIRA), also known as a sartan – e.g. valsartan, telmisartan, irbesartan, especially if you have kidney disorders related to diabetes;
  • aliskiren;
• if you are taking any of the following medicines, as the risk of angioedema may increase:
  • racecadotril, a medicine used to treat diarrhoea;
  • medicines used to prevent organ transplant rejection and in cancer treatment (e.g. temsirolimus, sirolimus, everolimus);
  • vildagliptin, a medicine used to treat diabetes.

Inform your doctor if you are pregnant, suspect you may be pregnant, or are planning a pregnancy. Rimal is not recommended during the first three months of pregnancy and must not be used after the 3rd month of pregnancy, as it may seriously harm the unborn child if taken during this period (see section "Pregnancy and breastfeeding").

Your doctor may recommend regular monitoring of white blood cell count, especially at the beginning of treatment, in patients with kidney function disorders or collagenosis, and also if medicines affecting blood cell count are being used.

Your doctor may recommend regular monitoring of kidney function, blood pressure, and blood electrolyte levels (e.g. potassium).

See also the section "When not to take Rimal".

Children and adolescents

Do not use Rimal in children and adolescents under 18 years of age due to lack of data on safety and efficacy in this patient group.

Rimal with other medicines

Tell your doctor or pharmacist about all medicines you are currently taking or have recently taken, as well as any you plan to take. This is necessary because Rimal may affect the action of other medicines, and other medicines may affect the action of Rimal.

Tell your doctor if you are taking any of the following medicines. These medicines may reduce the effect of Rimal:

• painkillers and anti-inflammatory medicines (e.g. non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, indometacin, or acetylsalicylic acid);
• medicines used for low blood pressure, shock, heart failure, asthma, or allergies, such as ephedrine, noradrenaline, adrenaline, dobutamine, or dopamine – your doctor will recommend regular blood pressure monitoring;
• rifampicin (an antibiotic used to treat tuberculosis);
• St. John's wort (a herbal medicine used to treat depression).

Tell your doctor if you are taking any of the following medicines. These medicines may increase the risk of side effects when taken together with Rimal:

• painkillers and anti-inflammatory medicines (e.g. non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, indometacin, or acetylsalicylic acid);
• anticancer medicines (used in chemotherapy), such as temsirolimus;
• medicines used to prevent rejection of transplanted organs, such as tacrolimus or everolimus;
• diuretics (water tablets), such as furosemide;
• other blood pressure-lowering medicines, such as aliskiren;
• potassium supplements (including salt substitutes), potassium-sparing diuretics (such as spironolactone, triamterene, amiloride), and other medicines that increase potassium levels in the blood (e.g. trimethoprim and co-trimoxazole, used for bacterial infections; cyclosporine, an immunosuppressive medicine used to prevent organ transplant rejection; and heparin (used to thin the blood to prevent clots)) – close monitoring of blood potassium levels is required when these medicines are used together;
• corticosteroid anti-inflammatory medicines, such as prednisolone;
• allopurinol (used to reduce uric acid levels in the blood);
• procainamide (used for heart rhythm disorders);
• medicines that may affect blood cell counts;
• ketoconazole, itraconazole (antifungal medicines);
• erythromycin, clarithromycin (used to treat bacterial infections);
• ritonavir, indinavir, nelfinavir (used to treat HIV-infected patients);
• verapamil, diltiazem (used to treat heart rhythm disorders and high blood pressure).

Tell your doctor if you are taking any of the following medicines. Rimal may affect the action of these medicines:

• antidiabetic medicines, such as oral glucose-lowering agents and insulin. Rimal may lower blood glucose levels. Blood glucose levels should be closely monitored during treatment with Rimal;
• lithium (used to treat psychiatric disorders). Rimal may increase lithium levels in the blood. Your doctor will recommend regular monitoring of blood lithium levels;
• simvastatin (a medicine that lowers blood cholesterol levels). Rimal may increase simvastatin levels in the blood.

Your doctor may recommend a dose adjustment and/or additional precautions:

• if you are taking an angiotensin II receptor antagonist (AIIRA) or aliskiren (see also sections "When not to take Rimal" and "Warnings and precautions").

If any of the above conditions apply to you (or if you have any doubts), speak to your doctor before taking Rimal.

Rimal with food, drink, and alcohol

Rimal can be taken with or without food.

Drinking alcohol while taking Rimal may cause dizziness or a feeling of "emptiness" in the head. If you have any doubts about how much alcohol you can consume while taking Rimal, consult your doctor, as alcohol and blood pressure-lowering medicines may intensify each other's effects.

Do not eat grapefruit or drink grapefruit juice while taking Rimal. This is because grapefruit and grapefruit juice may increase the blood concentration of the active substance amlodipine, which could lead to unpredictable intensification of the blood pressure-lowering effect of Rimal.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, suspect you may be pregnant, or are planning to have a child, consult your doctor or pharmacist before taking this medicine.

Do not use Rimal during the first 12 weeks of pregnancy and do not take it after the 12th week of pregnancy, as it may seriously harm the unborn child if used during this period. If you become pregnant while taking Rimal, inform your doctor immediately.

Your doctor will recommend an alternative medicine if you are planning a pregnancy.

Do not use Rimal during breastfeeding.

Driving and using machines

Rimal may affect your ability to drive or operate machinery, as dizziness, headache, and/or fatigue may occur during treatment. This is most likely at the beginning of treatment or when increasing the dose of Rimal. If such symptoms occur, do not drive or operate machinery.

3. How to take Rimal

This medicine should always be taken as directed by a physician or pharmacist. If in doubt,
consult a physician or pharmacist.
Instructions for use

• This medicine should be taken orally, at the same time each day, with or without food.
• Hard capsules must be swallowed whole with liquid (do not take with grapefruit juice); do not chew or crush them.

Dosage

• The usual dose is 1 capsule of the strength prescribed by the physician, taken once daily.
• Depending on the therapeutic response, the physician may adjust the dose.
• The maximum dose is 1 capsule of 10 mg + 10 mg once daily.

If you feel the effect of the medicine is too strong or too weak, inform your physician.
Elderly patients
Rimal is not recommended for use in elderly or debilitated patients.
Use in children and adolescents
Rimal must not be used in children and adolescents under 18 years of age due to lack of data on
safety and efficacy.
Taking more Rimal than recommended
If an overdose occurs, the following symptoms may occur: lowering of arterial blood pressure (even
severe), dizziness, sensation of "emptiness" in the head, fainting. If arterial blood pressure drops
to critical levels, shock with loss of consciousness may occur. Within 24–48 hours after taking the
medicine, shortness of breath may develop due to fluid accumulation in the lungs (pulmonary edema).
In case of overdose, seek immediate medical attention at a doctor's office or the nearest hospital
emergency department. Do not drive yourself; ask someone to take you or call an ambulance. Bring
the medicine packaging with you. This will help the doctor identify which medicine has been taken.
Missed dose of Rimal
If a dose is missed, take the next dose at the regular time. Do not take a double dose to make up for
the missed dose.
Stopping Rimal
Do not abruptly stop taking Rimal or change the prescribed dose without consulting your physician,
as this may lead to worsening of the condition.
If you have any further questions about the use of this medicine, consult your physician or pharmacist.

4. Possible adverse effects

Like any medicine, this medicine can cause adverse effects, although not everyone will experience them.
If any of the following severe adverse symptoms occur, stop taking
Rimal and contact your doctor immediately – urgent medical assistance may be required:

• swelling of the face, lips, tongue or throat causing difficulty in swallowing or breathing, as well as skin itching and rash. These may be symptoms of a severe allergic reaction to Rimal (angioedema);
• severe skin reactions, including rash, ulceration of the oral mucosa, worsening of a pre-existing skin disease, redness, blistering or peeling of the skin (Stevens-Johnson syndrome, toxic epidermal necrolysis or erythema multiforme), or other allergic reactions.

Contact your doctor immediately if any of the following occur:

• increased heart rate, irregular or stronger heartbeat (palpitations), chest pain, feeling of pressure in the chest, or more serious disturbances, including heart attack or stroke;
• shortness of breath or cough – these may be symptoms of lung disorders;
• easier bruising, prolonged bleeding time, various types of bleeding (e.g. bleeding gums), purple spots on the skin (purpura), or more frequent than usual infections, sore throat and fever, feeling of fatigue, fainting, dizziness or pale skin. These may be symptoms of blood or bone marrow disorders;
• severe upper abdominal pain radiating to the back – this may be a symptom of pancreatitis;
• fever, chills, fatigue, loss of appetite, abdominal pain, nausea, or yellowing of the skin or eyes (jaundice). These may be symptoms of liver disorders, such as hepatitis or liver damage;
• concentrated urine (dark in color), nausea or vomiting, muscle cramps, confusion and seizures, which may result from inappropriate ADH secretion (vasopressin, antidiuretic hormone).

Other adverse effects:
If any of the following adverse effects worsen or persist for longer than a few
days, inform your doctor.
Common (occur in fewer than 1 in 10 patients):

• palpitations (irregular or stronger heartbeat);
• headache, central dizziness, drowsiness;
• hypotension (abnormally low blood pressure), orthostatic hypotension (especially when standing up or sitting down quickly from a lying position), fainting, sudden flushing (especially of the face and neck);
• dry, persistent cough, bronchitis, sinusitis, shortness of breath;
• gastritis and/or enteritis, digestive disturbances, dyspepsia, abdominal pain, diarrhea, nausea or vomiting;
• skin rash, especially with skin nodules;
• chest pain, fatigue, edema (fluid accumulation in tissues);
• muscle pain, muscle cramps, ankle swelling;
• increased potassium levels in the blood, detected in blood tests.

Uncommon (occur in fewer than 1 in 100 patients):

• visual disturbances (including blurred vision, double vision);
• tinnitus (e.g. ringing in the ears);
• kidney function disorders, including acute kidney failure, disturbances in urination (increased frequency and volume of urine, nocturia), worsening of proteinuria, increased blood urea and creatinine levels (parameters indicating kidney function);
• joint pain, back pain;
• increased or decreased body weight;
• vestibular dizziness, tremor, unusual sensory sensations such as numbness, tingling, pricking, burning or stinging of the skin (paresthesia), reduced sensation (hypoesthesia), loss or disturbances of taste;
• low mood or mood changes, depression, anxiety, nervousness, restlessness, sleep disturbances, including insomnia or drowsiness;
• bronchospasm, including worsening of asthma, nasal congestion or rhinitis;
• pancreatitis (rarely fatal), increased pancreatic enzyme activity (indicating pancreatic function) detected in blood tests, intestinal angioedema (intestinal swelling), presenting with abdominal pain, vomiting and diarrhea, upper abdominal pain, including gastritis, changes in bowel rhythm (including diarrhea and constipation), heartburn, dryness of the oral mucosa;
• increased liver enzyme activity and/or bilirubin levels (parameters indicating liver function), detected in blood tests;
• decreased or loss of appetite (anorexia);
• fever, weakness, pain, malaise;
• transient erectile dysfunction, impotence, decreased libido in men and women, gynecomastia (breast enlargement in men);
• increased number of certain types of white blood cells (eosinophilia), detected in laboratory blood tests;
• angina or myocardial infarction, increased heart rate, cardiac arrhythmias, swelling of hands or feet;
• swelling of the face, lips, tongue or throat (angioedema), rarely fatal – see above, itching, excessive sweating, hair loss, purple spots on the skin (purpura), skin discoloration.

Rare (occur in fewer than 1 in 1,000 patients):

• disorientation;
• balance disorders;
• conjunctivitis;
• glossitis (inflammation of the tongue);
• skin inflammation with peeling, urticaria (itchy rash with skin blisters), nail plate separation from the nail bed;
• hearing disturbances;
• decreased number of red blood cells, white blood cells or platelets, or decreased hemoglobin concentration, detected in laboratory blood tests;
• narrowing of blood vessels, reduced blood flow through vessels, vasculitis (inflammation of blood vessels);
• cholestatic jaundice, liver cell damage.

Very rare (occur in fewer than 1 in 10,000 patients):

• increased blood glucose levels;
• hepatitis;
• photosensitivity reactions, erythematous-edematous skin changes and blister formation on the skin and mucous membranes (erythema multiforme, Stevens-Johnson syndrome) – see above;
• increased muscle tone;
• peripheral nerve disorders;
• gingival hyperplasia (overgrowth of the gums).

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

• concentration disturbances;
• inflammation of the oral mucosa with small ulcers (aphthous stomatitis);
• decreased sodium levels in the blood, detected in laboratory blood tests;
• concentrated urine (dark in color), nausea or vomiting, muscle cramps, confusion and seizures – syndrome of inappropriate antidiuretic hormone secretion – see above;
• color change of fingers of hands and feet in response to cold, followed by tingling or pain upon warming (Raynaud's phenomenon);
• cerebral circulation disorders, including stroke, slowed or disturbed reactions, burning sensation, disturbances in smell;
• severe skin and mucous membrane disease with erythematous-edematous changes, blisters and detachment of large areas of epidermis (toxic epidermal necrolysis), blistering skin disease (pemphigus), exacerbation of psoriasis (skin disease with red, scaly lesions), other types of skin rashes or mucosal rashes;
• bone marrow failure, decreased number of all blood cells, anemia due to increased destruction of red blood cells (hemolytic anemia);
• severe allergic and non-allergic reactions (anaphylactic and pseudoanaphylactic reactions), positive antinuclear antibody titer (indicating connective tissue diseases);
• acute liver failure;
• tremor, postural rigidity, facial masking, slowed movements and dragging of legs while walking, unsteady gait.

Reporting of adverse effects
If any adverse effects occur, including any not listed
in this leaflet, inform your doctor or pharmacist. Adverse effects can be reported
directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse effects can also be reported to the marketing authorization holder.
Reporting adverse effects helps to provide more information on the safety of this medicine.

5. How to store Rimal medication

Keep this medicine out of sight and reach of children.
Do not store above 25°C.
Do not use this medicine after the expiry date stated on the carton and blister pack.
The marking on the packaging following EXP indicates the expiry date, and following Lot/LOT indicates the batch number.
The expiry date refers to the last day of the stated month.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This helps protect the environment.

6. Contents of the pack and other information

What Rimal contains

• The active substances are amlodipine and ramipril. Each hard capsule with a strength of 5 mg + 5 mg contains 5 mg of ramipril and 5 mg of amlodipine (as amlodipine besylate). Each hard capsule with a strength of 5 mg + 10 mg contains 5 mg of ramipril and 10 mg of amlodipine (as amlodipine besylate). Each hard capsule with a strength of 10 mg + 5 mg contains 10 mg of ramipril and 5 mg of amlodipine (as amlodipine besylate). Each hard capsule with a strength of 10 mg + 10 mg contains 10 mg of ramipril and 10 mg of amlodipine (as amlodipine besylate).
• Other ingredients are: microcrystalline cellulose, hypromellose, crospovidone (type B), glycerol dibehenate, gelatin, titanium dioxide (E171), indigo carmine (E132) (only in Rimal 5 mg + 5 mg, Rimal 5 mg + 10 mg, Rimal 10 mg + 10 mg).

What Rimal looks like and contents of the pack
Rimal 5 mg + 5 mg are hard, gelatin, light blue capsules filled with white or almost white powder or lightly compressed agglomerate; capsule size – No. 3
Rimal 5 mg + 10 mg are hard, gelatin capsules with a white body and a blue cap, filled with white or almost white powder or lightly compressed agglomerate; capsule size – No. 1
Rimal 10 mg + 5 mg are hard, gelatin, white capsules filled with white or almost white powder or lightly compressed agglomerate; capsule size – No. 1
Rimal 10 mg + 10 mg are hard, gelatin, blue capsules filled with white or almost white powder or lightly compressed agglomerate; capsule size – No. 1
The pack contains 30, 60 or 90 hard capsules.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Zakłady Farmaceutyczne POLPHARMA S.A.
ul. Pelplińska 19
83-200 Starogard Gdański
tel. + 48 22 364 61 01