Ampril hd

Patient Information Leaflet

Ampril HL, 2.5 mg + 12.5 mg, tablets
Ampril HD, 5 mg + 25 mg, tablets
ramipril + hydrochlorothiazide
Please read this leaflet carefully before taking this medicine, because 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 patient only. Do not pass it on to others. It may harm them even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Table of Contents

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

1. What Ampril HL, Ampril HD is and what it is used for

Ampril HL, Ampril HD is a combination medicine containing ramipril and hydrochlorothiazide.
Ramipril belongs to a group of medicines called ACE inhibitors (angiotensin-converting enzyme inhibitors). This medicine works by:

• reducing the amount of substances produced by the body that increase blood pressure,
• relaxing and widening blood vessels,
• helping the heart to pump blood through the body more easily.

Hydrochlorothiazide belongs to a group of medicines called thiazide diuretics or water pills. This medicine works by increasing the amount of water (urine) the body gets rid of, which helps lower blood pressure.
Ampril HL, Ampril HD is used to treat high blood pressure (hypertension). Both active substances work together to lower blood pressure. These substances are used in combination when treatment with only one of them is not effective enough.

2. Important information before using Ampril HL, Ampril HD

When not to use Ampril HL, Ampril HD

• if the patient is allergic to ramipril, hydrochlorothiazide, or any of the other ingredients of this medicine (listed in section 6);
• if the patient is allergic (hypersensitive) to medicines similar to Ampril HL, Ampril HD (other ACE inhibitors or sulfonamide derivatives). Symptoms of an allergic reaction may include rash, difficulty swallowing or breathing, swelling of lips, face, throat or tongue;
• if the patient has ever had a severe allergic reaction called angioedema. Symptoms include itching, hives, red spots on hands, feet and throat, swelling of throat and tongue, swelling around eyes and lips, difficulty breathing and swallowing;
• if the patient is undergoing dialysis or another blood filtration procedure. Depending on the equipment used, Ampril HL, Ampril HD may not be suitable;
• if severe liver disease has been diagnosed;
• if there are abnormal levels of electrolytes (calcium, potassium, sodium) in the blood;
• if there are kidney disorders involving reduced blood flow to the kidneys (renal artery stenosis);
• during the last 6 months of pregnancy (see below, section "Pregnancy and breastfeeding");
• during breastfeeding (see below, section "Pregnancy and breastfeeding");
• if the patient has diabetes or kidney problems and is being treated with a blood pressure-lowering medicine containing aliskiren;
• if the patient has taken or is currently using sacubitril with valsartan, a medicine used to treat certain types of chronic (long-term) heart failure in adults, because the risk of angioedema (rapid swelling of tissues under the skin, such as in the throat) increases.

Do not take Ampril HL, Ampril HD if any of the above situations apply to the patient. If in doubt, consult a doctor before using Ampril HL, Ampril HD.

Warnings and precautions

Before starting treatment with Ampril HL, Ampril HD, discuss with your doctor or pharmacist:

• if there are disorders of the heart, liver or kidneys;
• in case of significant loss of electrolytes or fluids (due to vomiting, diarrhoea, excessive sweating, low-salt diet, prolonged use of diuretics or dialysis);
• if undergoing allergy desensitisation treatment for bee or wasp stings;
• if anaesthetic agents are to be administered. These may be used during surgical or dental procedures. It may be necessary to stop taking Ampril HL, Ampril HD one day before the scheduled procedure; consult your doctor;
• if high potassium levels in the blood have been diagnosed (based on blood test results);
• if the patient has a connective tissue disease such as scleroderma or systemic lupus erythematosus;
• if the patient has previously had skin cancer or if unexpected skin changes occur during treatment. Treatment with hydrochlorothiazide, especially in high doses over a long period, may increase the risk of certain types of non-melanoma skin cancer and lip cancer. While taking Ampril HL, Ampril HD, protect the skin from sunlight and UV radiation;
• if the patient previously experienced breathing or lung problems (including pneumonia or fluid accumulation in the lungs) after taking hydrochlorothiazide. If the patient develops severe shortness of breath or difficulty breathing after taking Ampril HL, Ampril HD, seek immediate medical help;
• if the patient is taking any of the following medicines, as the risk of angioedema (rapid swelling under the skin, such as in the throat) increases:
  • racecadotril, a medicine used to treat diarrhoea;
  • medicines used to prevent organ transplant rejection and to treat cancer (e.g. temsirolimus, sirolimus, everolimus);
  • vildagliptin, a medicine used to treat diabetes.
• if the patient is taking any of the following medicines used to treat high blood pressure:
  • an angiotensin II receptor antagonist (AIIRA), also known as a sartan – for example, valsartan, telmisartan, irbesartan, especially if the patient has kidney problems related to diabetes,
  • aliskiren. 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 use Ampril HL, Ampril HD".
• if the patient experiences blurred vision or eye pain. These may be symptoms of fluid accumulation in the vascular layer surrounding the eye (excessive fluid accumulation between choroid and sclera) or increased intraocular pressure, which may occur within hours to weeks after taking Ampril HL, Ampril HD. If untreated, these conditions may lead to permanent vision loss. Patients with a history of allergy to penicillin or sulfonamides may be at higher risk of developing this condition.

Inform your doctor if you are pregnant, suspect pregnancy, or are planning pregnancy. Use of Ampril HL, Ampril HD is not recommended during the first 3 months of pregnancy, and use after 3 months of pregnancy may cause severe harm to the unborn baby (see below, section "Pregnancy and breastfeeding").

Children and adolescents

Ampril HL, Ampril HD is not recommended for use in children and adolescents under 18 years of age. This medicine has never been studied in these age groups.

If any of the above situations apply to the patient (or if in doubt), consult a doctor before starting Ampril HL, Ampril HD.

Ampril HL, Ampril HD and other medicines

Tell your doctor or pharmacist about all medicines you are currently taking or have recently taken, including those obtained without a prescription (including herbal medicines). Ampril HL, Ampril HD may affect the action of other medicines. Likewise, other medicines may affect the action of Ampril HL, Ampril HD.

Inform your doctor if you are taking any of the following medicines. They may reduce the effectiveness of Ampril HL, Ampril HD:

• painkillers and anti-inflammatory medicines (e.g. non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen or indomethacin, and acetylsalicylic acid);
• medicines used to treat low blood pressure, shock, heart failure, asthma or allergies, such as ephedrine, noradrenaline or adrenaline. In such cases, your doctor will monitor your blood pressure.

Inform your doctor if you are taking any of the following medicines. They may increase the risk of adverse effects when used together with Ampril HL, Ampril HD:

• painkillers and anti-inflammatory medicines (e.g. non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen or indomethacin, and acetylsalicylic acid);
• medicines that reduce potassium levels in the blood. These include medicines for constipation, diuretics, amphotericin B (used to treat fungal infections), and ACTH (a hormone used in adrenal function testing);
• medicines used to treat cancer (chemotherapy);
• medicines used for heart conditions, including antiarrhythmics;
• medicines used to prevent rejection of transplanted organs, e.g. cyclosporine;
• diuretics such as furosemide;
• potassium supplements (including salt substitutes), potassium-sparing diuretics, and other medicines that increase potassium levels in the blood, such as spironolactone, triamterene, amiloride, potassium salts, heparin (used to thin the blood to prevent clots), trimethoprim, and co-trimoxazole also known as trimethoprim/sulfamethoxazole (used for bacterial infections);
• corticosteroid anti-inflammatory medicines, such as prednisolone;
• calcium supplements;
• allopurinol (used to reduce uric acid levels in the blood);
• procainamide (used for heart rhythm disorders);
• cholestyramine (used to reduce blood lipid levels);
• carbamazepine (used to treat epilepsy);
• racecadotril (a medicine used to treat diarrhoea);
• medicines commonly used to prevent rejection of transplanted organs (sirolimus, everolimus, temsirolimus and other mTOR inhibitors) or vildagliptin (used to treat diabetes). See section "Warnings and precautions".

Inform your doctor if you are taking any of the following medicines. Their effects may be altered when taking Ampril HL, Ampril HD:

• antidiabetic medicines, such as oral glucose-lowering medicines and insulin. Ampril HL, Ampril HD may reduce blood glucose levels. Blood glucose levels should be closely monitored during treatment with Ampril HL, Ampril HD;
• lithium (used to treat psychiatric disorders). Ampril HL, Ampril HD may increase lithium levels in the blood. Your doctor will closely monitor lithium levels in the blood;
• muscle relaxants;
• quinine (used to treat malaria);
• iodine-containing preparations, which may be used during X-ray examinations – conventional or during CT scans in hospital;
• penicillin (used to treat infections);
• oral anticoagulant medicines (oral anticoagulants), such as warfarin.

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

• if the patient is taking an angiotensin II receptor antagonist (AIIRA) or aliskiren (see also sections "When not to use Ampril HL, Ampril HD" and "Warnings and precautions").

If any of the above situations apply to the patient (or if in doubt), consult a doctor before starting Ampril HL, Ampril HD.

Tests

Consult your doctor or pharmacist before starting treatment:

• if tests for parathyroid function are planned. Ampril HL, Ampril HD may affect test results;
• if anti-doping tests are to be performed (in athletes). Ampril HL, Ampril HD may cause a positive result.

Taking Ampril HL, Ampril HD with food, drink and alcohol

• Drinking alcohol while taking Ampril HL, Ampril HD may cause dizziness or a feeling of "emptiness" in the head. If in doubt about how much alcohol may be consumed while taking Ampril HL, Ampril HD, consult your doctor, as blood pressure-lowering medicines and alcohol mutually enhance each other's effects.
• Ampril HL, Ampril HD can be taken with or without food.

Pregnancy and breastfeeding

Inform your doctor if you are pregnant, suspect pregnancy, or are planning pregnancy.

Do not take Ampril HL, Ampril HD during the first 12 weeks of pregnancy and do not take the medicine after week 13 of pregnancy, as use during pregnancy may harm the unborn baby.

If pregnancy occurs while taking Ampril HL, Ampril HD, inform your doctor immediately. Before planning pregnancy, switch to another medicine appropriate for use during pregnancy.

Do not take Ampril HL, Ampril HD during breastfeeding.

Before taking any medicine, consult your doctor or pharmacist.

Driving and using machines

Do not drive or operate machinery until you know how Ampril HL, Ampril HD affects you. Dizziness may occur while taking Ampril HL, Ampril HD. The risk of dizziness is higher when starting treatment with Ampril HL, Ampril HD or after increasing the dose. In such cases, do not drive, use tools or operate machinery.

Ampril HL, Ampril HD contains lactose and sodium

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

This medicine contains less than 1 mmol (23 mg) of sodium per tablet, meaning the medicine is considered "sodium-free".

3. How to use Ampril HL, Ampril HD

This medicine should always be taken as directed by a doctor or pharmacist. If in doubt,
consult a doctor or pharmacist.
Use of the medicine

• The medicine should be taken orally, at the same time every day, preferably in the morning.
• Tablets should be swallowed with liquid.
• Tablets must not be crushed or chewed.

Dosage
Treatment of arterial hypertension
The doctor will adjust the dose until blood pressure is controlled.
Elderly patients
The doctor will reduce the initial dose and gradually adjust the dosage.
Taking more than the recommended dose of Ampril HL, Ampril HD
If more than the recommended dose of Ampril HL, Ampril HD is taken, contact a doctor immediately
or go to the emergency department of the nearest hospital. Do not drive; the patient should be
taken by another person or an ambulance should be called. Take the medicine packaging along, so
the doctor will know which medicine has been taken.
Missing a dose of Ampril HL, Ampril HD
If a dose is missed, take the next dose at the usual time.
Do not take a double dose to make up for a missed tablet.
If there are any further doubts regarding the use of this medicine, consult a doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
If any of the following severe adverse effects occur,
treatment with Ampril HL, Ampril HD must be discontinued and medical advice must be sought immediately – urgent medical assistance may be required:

• swelling of the face, lips or throat, making swallowing or breathing difficult, as well as itching and rash. These may be symptoms of a severe allergic reaction to Ampril HL, Ampril HD;
• severe skin reactions, including rash, mouth ulcers, worsening of pre-existing skin disease, redness, blistering or peeling of the skin (e.g. Stevens-Johnson syndrome, toxic epidermal necrolysis or erythema multiforme);
• acute respiratory failure (symptoms include severe shortness of breath, fever, weakness and confusion) (very rare (may occur in less than 1 in 10,000 patients)).

Seek immediate medical advice if any of the following occur:

• rapid heartbeat, irregular or forceful heartbeats (palpitations), chest pain, feeling of chest tightness or other serious disturbances, including heart attack and stroke;
• shortness of breath, cough, fever lasting 2 to 3 days and reduced appetite. These may be symptoms of lung disease, including pneumonia;
• easier bruising, longer than usual bleeding time, any signs of bleeding (e.g. bleeding gums), purple spots on the skin, or more frequent infections, sore throat and fever, fatigue, fainting, dizziness or pale skin. These may be symptoms of blood or bone marrow disorders;
• severe pain in the upper abdomen, which may radiate to the back. This may be a symptom of pancreatitis;
• fever, chills, fatigue, loss of appetite, stomach pain, nausea, yellowing of the skin or eyes (jaundice). These may be symptoms of liver disorders, such as hepatitis or liver damage.

Other adverse effects include:
Inform your doctor if any of the following symptoms worsen or persist for more than a few days.
Common (may affect up to 1 in 10 patients):

• Headache, weakness or fatigue.
• Dizziness. Dizziness is more likely when starting treatment with Ampril HL, Ampril HD and after increasing the dose.
• Dry, irritating cough or bronchitis.
• Higher than usual blood glucose levels, detected in laboratory tests. In patients with diabetes, this may worsen the condition.
• Higher than usual levels of uric acid or fats (lipids) in the blood, detected in laboratory tests.
• Pain, redness and swelling of joints.

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

• Skin rash with or without skin nodules.
• Sudden flushing (especially of the face and neck), fainting, hypotension (abnormally low blood pressure), particularly when standing up or sitting down quickly.
• Balance disturbances (vestibular dizziness).
• Itching and unusual skin sensations such as numbness, tingling, pricking, burning or stinging of the skin (paresthesia).
• Loss or disturbances of taste.
• Sleep disturbances.
• Low mood, anxiety, nervousness or irritability more than usual.
• Nasal congestion, sinusitis, shortness of breath.
• Gingivitis, swelling of the mouth.
• Redness, itching, swelling or watering of the eyes.
• Ringing in the ears.
• Blurred vision.
• Hair loss.
• Chest pain.
• Muscle pain.
• Constipation, stomach or intestinal pain.
• Indigestion or nausea.
• Passing a larger than usual amount of urine over 24 hours.
• Excessive sweating or thirst.
• Loss or decrease in appetite (anorexia), reduced appetite.
• Rapid or irregular heartbeat.
• Swelling of arms and legs. These may be symptoms of the body retaining more fluid than usual.
• Fever.
• Sexual dysfunction in men.
• Decreased number of red blood cells, white blood cells or platelets or decreased hemoglobin concentration, detected in laboratory tests.
• Liver, pancreas or kidney function abnormalities, detected in blood tests.
• Decreased potassium concentration in the blood, detected in laboratory tests.

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

• Vomiting, diarrhea or heartburn.
• Redness and swelling of the tongue or dryness of the oral mucosa.

Unknown (frequency cannot be estimated from the available data):

• Skin and lip cancers (non-melanoma skin cancers).
• Concentrated urine (dark in color), nausea or vomiting, muscle cramps, confusion and seizures, which may be symptoms of inappropriate antidiuretic hormone (ADH) secretion.
• If these symptoms occur, seek immediate medical advice.

Other reported adverse effects:
Inform your doctor if any of the following symptoms worsen or persist for more than a few days.

• Difficulty concentrating, restlessness or confusion.
• Change in color of fingers and toes when cold, and tingling or pain when warming up. This may be Raynaud's phenomenon.
• Breast enlargement in men.
• Blood clots.
• Hearing disturbances.
• Reduced tear production in the eyes.
• Seeing yellow.
• Visual impairment or eye pain due to increased pressure (possible symptoms of fluid accumulation in the vascular layer surrounding the eye – excessive accumulation of fluid between choroid and sclera – acute myopia or acute angle-closure glaucoma).
• Dehydration.
• Swelling, pain and redness of the cheeks (sialadenitis).
• Intestinal swelling, known as angioedema of the intestine, manifesting as abdominal pain, vomiting and diarrhea.
• Increased sensitivity to sunlight.
• Severe skin peeling, itchy nodular rash or other skin reactions, such as red rash on the face or forehead.
• Skin rash or bruising.
• Skin spots and cold extremities.
• Nail disorders (e.g. separation of the nail plate from the nail bed).
• Musculoskeletal stiffness or inability to move the jaw (tetany).
• Muscle weakness or cramps.
• Decreased libido in men or women.
• Presence of blood in the urine. This may be a symptom of kidney disease (interstitial nephritis).
• Increased glucose in the urine.
• Increased number of certain white blood cells (eosinophilia), detected in blood tests.
• Too few blood cells (pancytopenia), detected in blood tests.
• Changes in electrolyte concentrations, such as sodium, calcium, magnesium and chloride in the blood, detected in blood tests.
• Slowed or disturbed reflexes.
• Smell disturbances.
• Difficulty breathing or worsening of asthma.

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, 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 effects can also be reported to the marketing authorization holder.
Reporting adverse effects helps provide more information on the safety of the medicine.

5. How to store Ampril HL, Ampril HD

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging following the word EXP. The expiry date refers to the last day of the specified month.
Do not store above 30°C.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the packaging and other information

What Ampril HL, Ampril HD contains

• The active substances are ramipril and hydrochlorothiazide.
  Ampril HL: Each tablet contains 2.5 mg ramipril and 12.5 mg hydrochlorothiazide.
  Ampril HD: Each tablet contains 5 mg ramipril and 25 mg hydrochlorothiazide.
• Other ingredients are: sodium bicarbonate, lactose monohydrate, sodium croscarmellose, pregelatinized starch, and sodium stearyl fumarate. See section 2 "Ampril HL, Ampril HD contains lactose and sodium".

What Ampril HL, Ampril HD looks like and contents of the pack
Ampril HL: white to off-white, uncoated, flat, capsule-shaped tablets with a score line on one side, marked "12.5". The score line is intended only to facilitate breaking the tablet for easier swallowing and does not indicate division into equal doses.
Ampril HD: white to off-white, uncoated, flat, capsule-shaped tablets with a score line on one side and on the edges, marked "25". The tablet can be divided into equal doses.
Pack sizes: 30 tablets in blisters, packed in a cardboard box.

Marketing Authorisation Holder and Manufacturer
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia