Parvati

Package leaflet: Information for the user

Parvati 2.5 mg + 5 mg hard capsules, 5 mg + 5 mg hard capsules, 10 mg + 5 mg hard capsules, 5 mg + 10 mg hard capsules, 10 mg + 10 mg hard capsules

Ramipril/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 you, because it may be harmful.
• If you experience any adverse reaction, including those not listed in this leaflet, contact your doctor or pharmacist.

Contents of this leaflet

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

1. What Parvati is and what it is used for

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

• relaxing and widening blood vessels so that blood can flow more easily. Ramipril works by:
• reducing the body's production of substances that can raise blood pressure;
• relaxing and widening blood vessels;
• making it easier for the heart to pump blood around the body.

Parvati is used for the treatment of hypertension (high blood pressure) in patients whose blood pressure is adequately controlled with amlodipine and ramipril taken simultaneously at the same dose as in Parvati, but as separate medicines.

2. What you should know before taking Parvati

Do not take Parvati:

• if you are allergic to amlodipine, ramipril (active substances), any other calcium antagonist, or any other ACE inhibitor, or to any of the other ingredients of this medicine (listed in section 6). The reaction may include itching, skin redness, or difficulty breathing;
• if your blood pressure is unusually low or unstable. Your doctor will need to assess this;
• if you have narrowing of the heart's aortic valve (aortic stenosis) or cardiogenic shock (a condition in which the heart is unable to supply sufficient blood to the body);
• if you have heart failure following a heart attack;
• if you have ever had a severe allergic reaction called "angioedema." Signs include: itching, hives, red spots on the hands, feet and throat, swelling of the throat and tongue, swelling around the eyes and lips, difficulty breathing and swallowing;
• if you are on dialysis or undergoing any other type of blood filtration. Depending on the machine used, Parvati may not be suitable for you;
• if you have kidney problems caused by reduced blood flow to the kidneys (renal artery stenosis);
• during the last 6 months of pregnancy (see section "Pregnancy and breastfeeding");
• if you have diabetes or impaired kidney function and are being treated with a blood pressure-lowering medicine containing aliskiren;
• if you have taken or are currently taking sacubitril/valsartan, a medicine used to treat a type of long-term (chronic) heart failure in adults, as this increases the risk of angioedema (rapid swelling under the skin, such as in the throat);
• if you are taking any of the following medicines, as the risk of angioedema may be increased:
  • racecadotril, a medicine used to treat diarrhoea;
  • medicines used to prevent rejection of transplanted organs and to treat cancer (such as temsirolimus, sirolimus, everolimus);
  • vildagliptin, a medicine used to treat diabetes.

Do not take Parvati if any of the above conditions apply to you. If you are unsure, consult your doctor or pharmacist before taking Parvati.

Warnings and precautions

Talk to your doctor or pharmacist before taking Parvati. Inform your doctor if any of the following apply to you:

• if you have high blood pressure (hypertensive crisis);
• if you are elderly and your dosage needs to be increased;
• if you have heart, liver, or kidney problems;
• if you have lost significant amounts of salts or body fluids (due to illness such as vomiting, diarrhoea, excessive sweating, or due to a low-salt diet, or after long-term use of oral diuretics, or following dialysis);
• if you are about to undergo treatment to reduce allergy to bee or wasp stings (desensitisation);
• if you are about to be treated with an anaesthetic. This may be administered during surgery or dental procedures. You must stop taking Parvati one day before; consult your doctor for further information;
• if you have high levels of potassium in your blood (shown by a blood test);
• if you have a vascular collagen disease such as scleroderma or systemic lupus erythematosus;
• if you are taking any of the following medicines for 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 information under "Do not take Parvati".

Children and adolescents

The use of Parvati is not recommended in children and adolescents under 18 years of age, as there is no available information for this patient population.

Other medicines and Parvati

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

In particular, inform your doctor or pharmacist if you are taking, have recently taken, or might take any of the following medicines:

• Potassium supplements (including salt substitutes), potassium-sparing diuretics, and other medicines that may increase potassium levels in the blood (such as trimethoprim and cotrimoxazole used to treat bacterial infections);
• cyclosporine, an immunosuppressant medicine used to prevent rejection of transplanted organs;
• heparin, a medicine used to thin the blood and prevent blood clots.

Inform your doctor if you are taking any of the following medicines, as they may reduce the effectiveness of Parvati:

• Medicines used to relieve pain and inflammation (e.g. non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen or indomethacin, and aspirin);
• Medicines used to treat low blood pressure, shock, heart failure, asthma, or allergies, such as ephedrine, noradrenaline, or adrenaline. Your doctor will need to monitor your blood pressure;
• rifampicin (an antibiotic used to treat tuberculosis);
• Hypericum perforatum (St. John’s wort, used to treat depression).

Inform your doctor if you are taking any of the following medicines, as they may increase the likelihood of side effects when taken with Parvati:

• Medicines used to relieve pain and inflammation (e.g. non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen or indometacine, and aspirin);
• Medicines for cancer (chemotherapy);
• Medicines to prevent rejection of transplanted organs, such as cyclosporine;
• Diuretics such as furosemide;
• Medicines that increase potassium levels in the blood, such as spironolactone, triamterene, amiloride, potassium salts, and heparin (to thin the blood);
• Steroid medicines for inflammation, such as prednisolone;
• Allopurinol (used to lower uric acid levels in the blood);
• Procainamide (for heart rhythm problems);
• Ketoconazole, itraconazole (antifungal medicines);
• Ritonavir, indinavir, nelfinavir (so-called protease inhibitors, used to treat HIV virus);
• Erythromycin, clarithromycin (antibiotics for bacterial infections);
• Verapamil, diltiazem (medicines for heart conditions or high blood pressure);
• Vildagliptin (an oral medicine that lowers glucose levels);
• Dantrolene (an infusion medicine for severe body temperature disorders);
• Trimethoprim and cotrimoxazole (for bacterial infections);
• Temsirolimus (for cancer);
• Everolimus (to prevent rejection of grafts);
• Tacrolimus (used to control the immune response, allowing the body to accept a transplanted organ).

Inform your doctor if you are taking any of the following medicines, as their effects may be altered by Parvati:

• Medicines for diabetes, such as oral medicines to lower blood sugar levels and insulin. Parvati may lower blood sugar levels. Monitor your blood sugar levels while taking Parvati;
• Lithium (for mental health conditions). Parvati may increase lithium levels in the blood. Your doctor must closely monitor your blood lithium levels;
• Simvastatin (a medicine to lower cholesterol). Parvati may increase simvastatin levels in the blood.

Your doctor may consider it necessary to adjust the dose and/or take other precautions:

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

If any of the above situations apply to you (or if you are unsure), inform your doctor before taking Parvati.

Parvati with food, drinks, and alcohol

Parvati can be taken with or without food.

People taking Parvati must not consume grapefruit or grapefruit juice. This is because grapefruit and grapefruit juice can increase blood levels of the active substance amlodipine, thereby enhancing the effect of Parvati and causing an unpredictable drop in blood pressure.

Drinking alcohol with Parvati may cause dizziness or confusion. If you are concerned about how much alcohol you can drink while taking Parvati, talk to your doctor, as blood pressure-lowering medicines and alcohol may have additive effects.

Pregnancy, breastfeeding, and fertility

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

Pregnancy

Do not take Parvati during pregnancy.

If you think you may be pregnant while taking Parvati, inform your doctor immediately. Before planning a pregnancy, you should switch to an alternative therapy appropriate for pregnancy.

Breastfeeding

It has been shown that amlodipine passes into breast milk in small amounts.

Do not take Parvati if you are breastfeeding. Inform your doctor or pharmacist before taking any medicine.

Driving and using machines

Parvati may affect your ability to drive or operate machinery. If Parvati causes you discomfort, dizziness or fatigue, or headache, do not drive or operate machinery and contact your doctor immediately. This may especially occur at the beginning of treatment or when switching from other medicines.

Parvati contains Sodium

This medicine contains less than 1 mmol (23 mg) of sodium per capsule, i.e. essentially 'sodium-free'.

3. How to take Parvati

Take this medicine exactly as instructed by your doctor or pharmacist.
If you have any doubts, consult your doctor or pharmacist.
If you feel that the effect of Parvati is too strong or too weak, inform your doctor or pharmacist.

Take the medicine orally at the same time each day, with or without food. Swallow the capsule whole with liquid.
Do not break or chew the capsules.
Do not take Parvati with grapefruit juice.
Parvati should be taken once daily.
Your doctor may adjust the dose depending on how it affects you. The maximum daily dose is one 10 mg + 10 mg capsule.

Elderly
Your doctor will reduce the initial dose and adjust treatment more gradually.

Use in children and adolescents
The use of Parvati is not recommended in children and adolescents under 18 years of age, as information for this patient population is not available.

If you take more Parvati than you should
Taking too many capsules may cause a drop in blood pressure, possibly a dangerous one. You may experience dizziness, lightheadedness, fainting, or weakness. If the drop in blood pressure is severe, shock may occur. The skin may become cold and clammy, and you may lose consciousness. Contact your doctor immediately or go immediately to the nearest hospital. Do not drive yourself to the hospital; have someone drive you or call an ambulance. Take the medicine package with you so the doctor knows what you have taken.

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 forget to take Parvati
If you forget to take a capsule, skip that dose completely and take the next dose at your usual time. Do not take a double dose to make up for the missed capsule.

If you stop taking Parvati
Your doctor will inform you how long you should take this medicine. If you stop treatment before being told to do so, your condition may return.

If you have any questions 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.
If you notice any of the following serious side effects, stop treatment with Parvati and consult your doctor immediately, as you may require urgent medical treatment:

• swelling of the face, lips or throat causing difficulty in swallowing or breathing, together with itching and skin rash. This could be a sign of a severe allergic reaction to Parvati;
• severe skin reactions including rash, mouth ulcers, worsening of a pre-existing skin disease, redness, blisters or peeling of the skin (such as Stevens-Johnson syndrome, toxic epidermal necrolysis or erythema multiforme), or other allergic reactions.

Contact your doctor immediately if you experience:

• a fast, irregular or strong heartbeat (palpitations), chest pain, tightness in the chest, or more serious problems including heart attack and stroke;
• shortness of breath or cough. This could be a sign of lung problems;
• increased tendency to bruise, bleeding that lasts longer than usual, any sign of bleeding (e.g. bleeding gums), purple spots, patches on the skin or increased susceptibility to infections, sore throat and fever, feeling tired, weak, dizzy or pale. These may be signs of blood or bone marrow problems;
• severe stomach pain that may radiate to the back. This could be a sign of pancreatitis (inflammation of the pancreas);
• fever, chills, fatigue, loss of appetite, stomach pain, feeling unwell, yellowing of the skin or eyes (jaundice). These may be signs of liver problems, such as hepatitis (liver inflammation) or liver damage.

Other side effects include:
Inform your doctor if any of the following side effects become severe or persist for more than a few days.

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

• drowsiness (particularly at the beginning of treatment);
• palpitations (awareness of a strong or rapid heartbeat), hot flushes;
• swelling of the ankles (oedema);
• headache or feeling tired;
• dizziness. This is more likely at the beginning of treatment with Parvati or when starting a higher dose;
• fainting, hypotension (low blood pressure), particularly when standing up or sitting down too quickly;
• dry, irritating cough, inflammation of the sinuses (sinusitis) or bronchitis, shortness of breath;
• abdominal pain, stomach ache or discomfort, diarrhoea, indigestion, feeling sick or vomiting;
• skin rash with or without swelling;
• chest pain;
• muscle cramps or muscle pain;
• blood tests showing abnormally high levels of potassium in the blood.

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

• mood changes, insomnia;
• tremors, weakness, pain, feeling unwell;
• visual disturbances, double vision, blurred vision, ringing in the ears;
• cold or runny nose due to inflammation of the nasal mucosa (rhinitis);
• changes in bowel habits (including diarrhoea or constipation), heartburn, dry mouth;
• hair loss, increased sweating, itchy skin, red spots on the skin, skin discoloration;
• problems with urination, increased need to urinate, especially at night, increased frequency of urination;
• inability to achieve an erection, sexual dysfunction in men, reduced sexual desire in men or women;
• breast discomfort or enlargement in men;
• joint or muscle pain, muscle cramps, back pain;
• weight gain or weight loss;
• balance problems (dizziness);
• itching and unusual skin sensations such as numbness, tingling, tickling, burning or chills (paraesthesia), loss of pain sensation;
• loss or change in taste;
• sleep problems;
• feeling depressed, anxious, more nervous than usual or restless;
• stuffy nose, difficulty breathing or worsening of asthma;
• intestinal swelling called “intestinal angioedema” presenting with symptoms such as abdominal pain, vomiting and diarrhoea;
• loss or decrease in appetite (anorexia);
• increased or irregular heartbeat;
• swollen arms and legs. This could be a sign that your body is retaining more fluid than normal;
• fever;
• an increase in a certain type of white blood cells (eosinophilia), detected during a blood test;
• blood tests showing changes in liver, pancreas or kidney function.

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

• sensation of trembling or confusion;
• red or swollen tongue;
• severe peeling or shedding of the skin, itching, skin rash with swelling;
• nail problems (e.g. loss or separation of a nail from the nail bed);
• skin rash or bruising;
• hives (urticaria);
• skin patches and hands, cold extremities;
• red, itchy, swollen or watery eyes;
• hearing disorders;
• blood tests showing a reduction in the number of red blood cells, white blood cells, platelets or haemoglobin levels.

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

• increased sensitivity to sunlight;
• excessive blood sugar levels (hyperglycaemia);
• swollen gums;
• abdominal swelling (gastritis);
• liver function abnormalities, liver inflammation (hepatitis), yellowing of the skin (jaundice);
• increased muscle tension;
• inflammation of blood vessels, often with skin rash;
• light sensitivity;
• disorders combining stiffness, tremors and/or movement disturbances;
• psoriasis.

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

• concentrated urine (dark in colour), feeling unwell or malaise, muscle cramps, confusion and seizures which may be due to inappropriate secretion of ADH (anti-diuretic hormone [antidiuretic hormone]). If you experience these symptoms, contact your doctor promptly;
• tremor, rigid posture, mask-like facial expression, slow movements and a shuffling gait.

Other reported side effects:
Inform your doctor if any of the following side effects become severe or last longer than a few days:

• difficulty concentrating;
• blood tests showing abnormally low levels of blood cells;
• blood tests showing abnormally low levels of sodium in the blood;
• fingers of hands and feet changing colour in the cold, followed by tingling or painful sensations when warming up (Raynaud's phenomenon);
• slowed or altered reactions;
• changes in the perception of smells.

Reporting of side effects
If you get any side effects, 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 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 Parvati

Keep this medicine out of the sight and reach of children.
Store below 30°C.
Keep in the original packaging to protect the medicine from light.
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.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Parvati contains
The active substances are:
Parvati 2.5 mg + 5 mg hard capsules
Each capsule contains: 2.5 mg ramipril and 6.934 mg amlodipine besilate (equivalent to 5 mg amlodipine).
Parvati 5 mg + 5 mg hard capsules
Each capsule contains: 5 mg ramipril and 6.934 mg amlodipine besilate (equivalent to 5 mg amlodipine).
Parvati 10 mg + 5 mg hard capsules
Each capsule contains: 10 mg ramipril and 6.934 mg amlodipine besilate (equivalent to 5 mg amlodipine).
Parvati 5 mg + 10 mg hard capsules
Each capsule contains: 5 mg ramipril and 13.868 mg amlodipine besilate (equivalent to 10 mg amlodipine).
Parvati 10 mg + 10 mg hard capsules
Each capsule contains: 10 mg ramipril and 13.868 mg amlodipine besilate (equivalent to 10 mg amlodipine).

The other components are: Microcrystalline cellulose, anhydrous calcium hydrogen phosphate, pregelatinized starch, low moisture pregelatinized starch, sodium starch glycolate (type A), sodium stearyl fumarate, red iron oxide (E172), titanium dioxide (E171), gelatin.
Parvati 10 mg + 10 mg also contains: yellow iron oxide (E172), black iron oxide (E172).

Description of the appearance of Parvati and pack sizes
Parvati 2.5 mg + 5 mg hard capsules: Hard gelatin capsules with an opaque pale pink cap and an opaque white body. Capsule contents: white or almost white powder.
Parvati 5 mg + 5 mg hard capsules: Hard gelatin capsules with an opaque pink cap and an opaque white body. Capsule contents: white or almost white powder.
Parvati 10 mg + 5 mg hard capsules: Hard gelatin capsules with an opaque dark pink cap and an opaque white body. Capsule contents: white or almost white powder.
Parvati 5 mg + 10 mg hard capsules: Hard gelatin capsules with an opaque red-brown cap and an opaque white body. Capsule contents: white or almost white powder.
Parvati 10 mg + 10 mg hard capsules: Hard gelatin capsules with an opaque brown cap and an opaque white body. Capsule contents: white or almost white powder.

Parvati is available in blisters containing 28 capsules.

Marketing Authorization Holder
Neopharmed Gentili S.p.A. – Via San Giuseppe Cottolengo, 15 – 20143 Milan, Italy

Manufacturers

• Special Product’s Line S.p.A. - Via Fratta Rotonda Vado Largo, 1 - 03012 Anagni (FR), Italy
• Lachifarma S.p.A. Laboratorio Chimico Farmaceutico Salentino - S.S. 16 - Zona Industriale 73010 Zollino (LE), Italy