Perindopril and indapamide Mylan: detailed information

Patient Information Leaflet

Perindopril and Indapamide Mylan 2.5 mg/0.625 mg film-coated tablets, 5 mg/1.25 mg film-coated tablets

perindopril arginine and indapamide
Generic Medicine
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 they have the same symptoms as you, because it may be harmful.
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Perindopril and Indapamide Mylan is and what it is used for

Perindopril and Indapamide Mylan is a combination of two active substances, perindopril and indapamide. It is an antihypertensive medicine used to treat high blood pressure (hypertension).
Perindopril belongs to a class of medicines called angiotensin-converting enzyme (ACE) inhibitors. These work by dilating blood vessels, making it easier for the heart to pump blood through them. Indapamide is a diuretic. Diuretics increase the amount of urine produced by the kidneys. Each of the two active substances helps to reduce blood pressure, and together they act to control your blood pressure.

2. What you should know before taking Perindopril and Indapamide Mylan

Do not take Perindopril and Indapamide Mylan:

if you are allergic to perindopril or any other ACE inhibitor, to indapamide or any other sulfonamide, 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 while taking an ACE inhibitor, or if you or a family member has ever had these 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) (see "Warnings and precautions" and "Other medicines and Perindopril and Indapamide Mylan"). Sacubitril/valsartan must not be started until at least 36 hours have passed after the last dose of Perindopril and Indapamide Mylan. If treatment with sacubitril/valsartan is stopped, therapy with Perindopril and Indapamide Mylan must not be started until at least 36 hours have passed after the last dose of sacubitril/valsartan;
if you suffer from severe liver disease or a condition called hepatic encephalopathy (a degenerative brain disorder);
if you have severe kidney disease where blood flow to the kidneys is reduced (renal artery stenosis), or if you are undergoing dialysis or any other type of blood filtration.

Depending on the equipment used, Perindopril and Indapamide Mylan may not be suitable for you;

if your blood potassium levels are high or low;
if it is suspected that you may have decompensated heart failure (symptoms may include severe fluid retention and breathing difficulties);
if you are more than 3 months pregnant (it would also be advisable to avoid taking Perindopril and Indapamide Mylan during pregnancy – see section "Pregnancy and breastfeeding");
if you are breastfeeding;
Perindopril and Indapamide Mylan contains soybean oil. If you are allergic to peanuts or soy, do not use this medicine;
if you have diabetes or impaired kidney function and are being treated with a blood pressure-lowering medicine containing aliskiren.

Warnings and precautions
Talk to your doctor or pharmacist before taking Perindopril and Indapamide Mylan

if you have aortic stenosis (narrowing of the main blood vessel leaving the heart) or hypertrophic cardiomyopathy (a heart muscle disease), or renal artery stenosis (narrowing of the artery supplying blood to the kidneys);
if you have heart failure or other heart problems;
if you have kidney problems, or if you are on dialysis;
if you have liver problems;
if you have a collagen disease (skin disease) such as systemic lupus erythematosus or scleroderma;
if you have atherosclerosis (hardening of the arteries);
if you have hyperparathyroidism (a condition in which your parathyroid gland is overactive);
if you have gout;
if you have diabetes;
if you are on a low-sodium diet or use salt substitutes containing potassium;
if you are taking lithium or potassium-sparing diuretics (spironolactone, triamterene), as their use with Perindopril and Indapamide Mylan (see "Taking Perindopril and Indapamide Mylan with other medicines") should be avoided;
if you are taking any of the following medicines used to treat high blood pressure:
- an "angiotensin II receptor antagonist" (AIIRA), 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 blood electrolyte levels (e.g. potassium) at regular intervals.

See also the section "Do not take Perindopril and Indapamide Mylan"

if you are of Black origin, as you may have a higher risk of angioedema and this medicine may be less effective in lowering blood pressure compared to non-Black patients;
if you are a patient undergoing hemodialysis with high-flux dialysis membranes;
if you are taking any of the following medicines, which increase the risk of angioedema (rapid swelling beneath the skin, for example in the throat):
- racecadotril, a medicine used to treat diarrhoea;
- sirolimus, everolimus, temsirolimus and other medicines belonging to the class of mTOR inhibitors (used to prevent organ transplant rejection and in cancer treatment);
- sacubitril (available as a fixed-dose combination with valsartan), used to treat chronic heart failure;
- linagliptin, saxagliptin, sitagliptin, vildagliptin, and other medicines belonging to the class of DPP-4 inhibitors (gliptins) (used in diabetes treatment);
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 intraocular pressure and may occur from a few hours to several weeks after taking Perindopril and Indapamide Mylan. This may lead to permanent vision loss if untreated. If you previously had an allergy to penicillin or sulfonamide, you may be at higher risk;
if you have muscle disorders, including pain, tenderness, weakness, or muscle cramps;
if you have abnormally high levels of a hormone called aldosterone in your blood (primary hyperaldosteronism);
if you are elderly;
if you have experienced photosensitivity reactions;
if you have a severe allergic reaction with swelling of 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 and consult a doctor immediately.

Angioedema
Angioedema (a severe allergic reaction with swelling of the face, lips, tongue or throat, causing difficulty in swallowing or breathing) has been reported in patients treated with ACE inhibitors, including Perindopril and Indapamide Mylan. This may occur at any time during treatment. If you develop such symptoms, you must stop taking Perindopril and Indapamide Mylan and consult a doctor immediately. See also section 4.
You must inform your doctor if you think you are (or may become) pregnant. Perindopril and Indapamide Mylan is not recommended during early pregnancy and must not be taken if you are more than 3 months pregnant, as it may cause serious harm to your baby if taken during this period (see section "Pregnancy and breastfeeding").
When taking Perindopril and Indapamide Mylan, you must also inform your doctor or hospital staff if:

you are due to undergo anaesthesia and/or surgery;
you have recently had diarrhoea or vomiting or are dehydrated;
you are due to undergo dialysis or LDL cholesterol apheresis (removal of cholesterol from your body via a machine);
you are due to undergo desensitisation treatment to reduce the effects of an allergy to bee or wasp stings;
you are due to undergo medical tests requiring injection of an iodinated contrast medium (a substance that makes certain organs such as kidneys or stomach visible on X-rays);
if you experience changes in vision or pain in one or both eyes while taking Perindopril and Indapamide Mylan. This could be a sign of developing glaucoma, increased pressure in the eye(s). You must stop treatment with Perindopril and Indapamide Mylan and consult a doctor.

For athletes: Using this medicine without therapeutic need constitutes doping and may result in a positive anti-doping test.
Children and adolescents
Perindopril and Indapamide Mylan must not be given to children and adolescents.
Other medicines and Perindopril and Indapamide Mylan
Inform your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including those not requiring a prescription.
Do not take Perindopril and Indapamide Mylan if you are taking the following medicines:

lithium (used to treat manic disorder or depression);
aliskiren (a medicine used to treat hypertension) if you do not have diabetes mellitus or kidney problems;
potassium-sparing diuretics (e.g. triamterene, amiloride), potassium salts, or other medicines that may increase potassium levels in the body (such as heparin, a medicine used to thin the blood and prevent clotting; trimethoprim and co-trimoxazole, also known as trimethoprim/sulfamethoxazole, for bacterial infections);
estramustine (used in cancer therapy);
other medicines used to treat high blood pressure: angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers.

Treatment with Perindopril and Indapamide Mylan must not be started until at least 36 hours have passed after the last dose of sacubitril/valsartan. Treatment with sacubitril/valsartan must not be started until at least 36 hours have passed after the last dose of Perindopril and Indapamide Mylan.
Other medicines may interfere with treatment with Perindopril and Indapamide Mylan. Your doctor may need to adjust the dose and/or take other precautions. Inform your doctor if you are taking any of the following medicines, as caution may be required:

other medicines for treating high blood pressure;
potassium-sparing drugs used in heart failure treatment: eplerenone and spironolactone at doses between 12.5 mg and 50 mg daily;
anaesthetic medicines;
iodinated contrast media;
antibiotics used to treat bacterial infections (e.g. moxifloxacin, sparfloxacin, intravenous erythromycin);
methadone (used to treat addiction);
procainamide (for treating irregular heartbeat);
allopurinol (for treating gout);
mizolastine, terfenadine or astemizole (antihistamines for hay fever and other allergies);
corticosteroids used to treat various conditions including severe asthma and rheumatoid arthritis;
immunosuppressants used to treat autoimmune diseases or after organ transplantation to prevent rejection (e.g. cyclosporine, tacrolimus);
medicines for treating cancer;
intravenous erythromycin (an antibiotic);
halofantrine (used to treat certain types of malaria);
pentamidine (used to treat pneumonia);
injectable gold (for treating 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 for treating heart rhythm disorders (e.g. quinidine, hydroquinidine, disopyramide, amiodarone, sotalol, ibutilide, dofetilide, digitalis, bretylium);
cisapride, difemanil (used to treat gastrointestinal and digestive problems);
digoxin or other cardiac glycosides (for treating heart problems);
baclofen (for treating muscle stiffness occurring in diseases such as multiple sclerosis);
medicines for treating diabetes such as insulin, metformin or gliptins;
calcium, including calcium supplements;
stimulant laxatives (e.g. senna);
non-steroidal anti-inflammatory drugs (e.g. ibuprofen) or high-dose salicylates (e.g. acetylsalicylic acid (a substance present in many medicines used to relieve pain and reduce fever, as well as to prevent blood clotting));
intravenous amphotericin B (to treat serious fungal infections);
medicines for treating neurological disorders such as depression, anxiety and schizophrenia (e.g. tricyclic antidepressants or neuroleptics (such as amisulpride, sulpiride, sultopride, tiapride, haloperidol, droperidol));
vasodilators, including nitrates (substances that dilate blood vessels);
medicines used to treat low blood pressure, shock or asthma (e.g. ephedrine, noradrenaline or adrenaline);
tetracosactide (for treating Crohn's disease);
potassium supplements (including salt substitutes), potassium-sparing diuretics, and other medicines that may increase potassium levels in the blood (such as trimethoprim and co-trimoxazole for treating bacterial infections; cyclosporine, an immunosuppressive medicine used to prevent organ transplant rejection; and heparin, a medicine used to thin the blood and prevent clotting).

Treatment with Perindopril and Indapamide Mylan may be affected by other medicines. Your doctor may need to adjust the dose and/or take other precautions. These include:

if you are taking an angiotensin II receptor antagonist (AIIRA) or aliskiren (see also section "Do not take Perindopril and Indapamide Mylan" and "Warnings and precautions") or diuretics (medicines that increase the amount of urine produced by the kidneys). Medicines that are more often used to treat diarrhoea (racecadotril) or to prevent rejection of transplanted organs (sirolimus, everolimus, temsirolimus and other medicines belonging to the class of mTOR inhibitors). See section "Warnings and precautions". sacubitril/valsartan (used for chronic heart failure. See section "Do not take" and "Warnings and precautions". vildagliptin, a medicine used to treat diabetes. See section "Warnings and precautions".

Perindopril and Indapamide Mylan with food and drink
It is preferable to take Perindopril and Indapamide Mylan before a meal.
Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Pregnancy
You must inform your doctor if you think you are (or may become) pregnant. Your doctor will usually advise you to stop taking Perindopril and Indapamide Mylan before becoming pregnant or as soon as you find out you are pregnant, and will recommend taking another medicine instead of Perindopril and Indapamide Mylan. Perindopril and Indapamide Mylan is not recommended during early pregnancy and must not be taken if you are more than 3 months pregnant, as it may cause serious harm to your baby if taken after the third month of pregnancy.
Breastfeeding
You must not take Perindopril and Indapamide Mylan if you are breastfeeding. Inform your doctor immediately if you are breastfeeding or about to start breastfeeding.
Driving and using machines
Perindopril and Indapamide Mylan usually does not affect reflexes, but in some patients, side effects such as dizziness or weakness related to a drop in blood pressure may occur. If you experience such effects, your ability to drive or operate machinery may be impaired.
Perindopril and Indapamide Mylan contains lactose and soybean oil.
If your doctor has diagnosed you with an intolerance to certain sugars, such as lactose, contact your doctor before taking this medicine.
Do not use this medicine if you are allergic to peanuts or soy.
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e. essentially "sodium-free".

3. How to take Perindopril and Indapamide Mylan

Take this medicine exactly as your doctor or pharmacist has told you. If you are unsure, consult your doctor or pharmacist.
The recommended dose is one tablet once daily. Your doctor may decide to increase the dose to two tablets daily or adjust the dose if you have renal impairment. It is preferable to take the tablet in the morning and before a meal. Swallow the tablet with a glass of water.
The break line is intended to help you split the tablet if you have difficulty swallowing it whole, and not for dividing the tablet into equal doses.

If you take more Perindopril and Indapamide Mylan than you should
If you take too many tablets, contact your doctor or the nearest hospital emergency department immediately. The most likely effect in case of overdose is a drop in blood pressure. If a marked drop in blood pressure occurs (associated with nausea, vomiting, cramps, dizziness, drowsiness, confusion, changes in the amount of urine produced by the kidneys), it may help to lie down with your legs raised.

If you forget to take Perindopril and Indapamide Mylan
It is important to take the medicine every day, as regular treatment is more effective. However, if you forget to take a dose of Perindopril and Indapamide Mylan, take the next dose at your usual time. Do not take a double dose to make up for the missed dose.

If you stop taking Perindopril and Indapamide Mylan
Since treatment for high blood pressure usually lasts a lifetime, you must speak with your doctor before stopping the treatment.

If you have any doubts about how to use this medicine, consult 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 immediately and contact your doctor straight away if you experience
any of the following side effects, which may be serious.

Severe dizziness or fainting due to low blood pressure (common) (up to 1 in 10 people),
Bronchospasm (tightness of the chest, wheezing and shortness of breath) (uncommon) (up to 1 in 100 people),
Swelling of the face, lips, mouth, tongue or throat, difficulty breathing (angioedema) (see section 2 “Warnings and precautions”) (uncommon) (up to 1 in 100 people),
Severe skin reactions, such as erythema multiforme (a skin rash that often starts with itchy red patches on the face, arms or legs) or severe rash, hives, redness of the skin all over the body, intense itching, blisters, peeling and swelling of the skin, inflammation of mucous membranes (Stevens-Johnson syndrome) or other allergic reactions (very rare) (up to 1 in 10,000 people),
Cardiovascular disorders (irregular heartbeat, angina pectoris (chest, jaw and back pain caused by physical exertion), heart attack) (very rare) (up to 1 in 10,000 people),
Weakness in arms or legs, or speech problems which could be signs of a possible stroke (very rare) (up to 1 in 10,000 people),
Inflammation of the pancreas which may cause severe abdominal pain and backache accompanied by feeling unwell (very rare) (up to 1 in 10,000 people),
Yellowing of the skin or eyes (jaundice) which may be a sign of hepatitis (very rare) (up to 1 in 10,000 people),
Life-threatening irregular heartbeat (not known),
Brain disease caused by liver disease (hepatic encephalopathy) (not known),
Muscle weakness, cramps, tenderness or pain, particularly if at the same time you feel unwell or have a high fever, which may be due to abnormal muscle breakdown (not known).

In order of decreasing frequency, the side effects may include:

Common (up to 1 in 10 people): Low levels of potassium in the blood, skin reactions in people predisposed to allergies and asthmatic reactions, headache, dizziness, vertigo, tingling, vision disturbances, tinnitus (sensation of ringing in the ears), cough, shortness of breath (dyspnea), gastrointestinal disorders (nausea, vomiting, abdominal pain, taste disturbances, indigestion or difficulty digesting, diarrhea, constipation), allergic reactions (such as skin rashes, itching), cramps, feeling of fatigue,
Uncommon (up to 1 in 100 people): Mood changes, depression, sleep disorders, urticaria, purpura (small red spots on the skin), blistering rash, kidney disorders, impotence (inability to achieve or maintain an erection), sweating, elevated eosinophils (a type of white blood cells), changes in laboratory parameters: high blood potassium levels (reversible upon discontinuation), low sodium levels in the blood which may lead to dehydration and reduced blood pressure, drowsiness, fainting, palpitations (awareness of heartbeat), tachycardia (rapid heartbeat), hypoglycemia (very low blood sugar levels) in diabetic patients, vasculitis (inflammation of blood vessels), dry mouth, photosensitivity reactions (increased skin sensitivity to sunlight), arthralgia (joint pain), myalgia (muscle pain), chest pain, malaise, peripheral edema, fever, increased blood urea, increased blood creatinine, falls.
Rare (up to 1 in 1,000 people): Worsening of psoriasis, changes in laboratory parameters: low chloride levels in the blood, low magnesium levels in the blood, increased liver enzyme levels, high serum bilirubin levels, fatigue, skin redness, reduced or absent urine output, acute kidney failure. Dark-colored urine, feeling unwell (nausea) or general malaise (vomiting), muscle cramps, confusion and seizures. These symptoms may be related to a condition called SIADH (syndrome of inappropriate antidiuretic hormone secretion).
Very rare (up to 1 in 10,000 people): Confusion, eosinophilic pneumonia (a rare type of pneumonia), rhinitis (blocked or runny nose), severe kidney problems, changes in blood parameters such as decreased numbers of white and red blood cells, lower hemoglobin, reduced platelet count, elevated blood calcium levels, abnormal liver function.
Not known (frequency cannot be estimated from the available data): Abnormal ECG pattern, changes in laboratory parameters: elevated uric acid levels and elevated blood sugar levels, decreased vision (myopia), blurred vision, visual impairment, reduced vision or eye pain due to high pressure (possible signs of fluid accumulation in the vascular layer of the eye (choroidal effusion) or acute angle-closure glaucoma), abnormal color, numbness and pain in fingers or toes (Raynaud's phenomenon). If you suffer from systemic lupus erythematosus (a collagen disease), this may worsen.

Haematological, renal, hepatic or pancreatic disorders and changes in laboratory parameters (blood tests) may occur. Your doctor may prescribe laboratory tests to monitor your condition. If you experience any of these symptoms, consult your doctor immediately.
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 http://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 Perindopril and Indapamide Mylan

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, bottle, or blister.
After Exp. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Perindopril and Indapamide Mylan in the bottle must be used within 6 months after first opening
of the bottle.
Do not dispose of any 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 Perindopril and Indapamide Mylan contains
Perindopril and Indapamide Mylan 2.5 mg/0.625 mg
The active substances are perindopril arginine and indapamide. One tablet contains 2.5 mg of perindopril arginine and 0.625 mg of indapamide.
Perindopril and Indapamide Mylan 5 mg/1.25 mg
The active substances are perindopril arginine and indapamide. One tablet contains 5 mg of perindopril arginine and 1.25 mg of indapamide.

The other components are:
Core:
Colloidal anhydrous silica, lactose monohydrate (see section 2 "Perindopril and Indapamide Mylan contains lactose and soybean oil"), magnesium stearate, maltodextrin, povidone (K 30), sodium starch glycolate (Type A).
Film coating (Opadry AMB White OY-B-28920):
Lecithin (soybean) (E322) (see section 2 "Perindopril and Indapamide Mylan contains lactose and soybean oil"), polyvinyl alcohol, talc (E553b), titanium dioxide (E171), xanthan gum (E415).

Description of the appearance of Perindopril and Indapamide Mylan and contents of the pack
Perindopril and Indapamide Mylan 2.5 mg/0.625 mg are white, film-coated, capsule-shaped, biconvex tablets, marked with "P", a score line, and "I" on one side and "M", a score line, and "1" on the other side.
Perindopril and Indapamide Mylan 5 mg/1.25 mg are white, film-coated, capsule-shaped, biconvex tablets, marked with "PI" on one side and "M2" on the other side.

Perindopril and Indapamide Mylan 2.5 mg/0.625 mg is available in blisters of 10, 14, 30, 60, 90 and 100 film-coated tablets and in plastic bottles containing 30 film-coated tablets.
Perindopril and Indapamide Mylan 5 mg/1.25 mg is available in blisters of 10, 14, 30, 60, 90 and 100 film-coated tablets and in plastic bottles containing 30 film-coated tablets.
Not all pack sizes may be marketed.

Marketing Authorization Holder
Mylan S.p.A.
Via Vittor Pisani, 20
20124 Milan, Italy

Manufacturer
McDermott Laboratories Limited trading as Gerard Laboratories,
35/36 Baldoyle Industrial Estate, Grange Road, Dublin 13, Ireland
Mylan Hungary Kft, Mylan utca 1, Komárom, 2900, Hungary
Mylan Germany GmbH, Benzstrasse 1, Bad Homburg 61352, Germany