PRINIVIL PLUS 20 mg/12.5 mg TABLETS

2. What you need to know before you take Prinivil Plus

Do not take Prinivil Plus

• if you are allergic (hypersensitive) to lisinopril, hydrochlorothiazide or any of the other ingredients of this medicine (listed in section 6).
• if you are allergic (hypersensitive) to any sulphonamide-derived medicine or any other angiotensin-converting enzyme inhibitor (ACE inhibitor). If you are not sure which ones these are, consult your doctor.
• if you have been treated with medicines of the same group as lisinopril (ACE inhibitors) and have suffered allergic reactions such as swelling of the face, lips, tongue and/or throat, with difficulty swallowing or breathing. You should not take lisinopril/hydrochlorothiazide if you have had these types of reactions without a known cause or if you have been diagnosed with idiopathic or hereditary angioedema.
• if you are more than 3 months pregnant (it is also better to avoid this medicine at the beginning of pregnancy - see section Pregnancy).

• if you do not urinate.

• if you have diabetes or kidney problems and are being treated with a blood pressure-lowering medicine that contains 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 the risk of angioedema (rapid swelling under the skin in areas such as the throat) is high.
• if you are taking any of the following medicines, the risk of angioedema may increase:

• Racecadotril, a medicine used to treat diarrhea.
• Medicines used to prevent organ transplant rejection and for cancer (e.g. temsirolimus, sirolimus, everolimus).
• Vildagliptin, a medicine used to treat diabetes.

Consult your doctor if you are not sure if you should start taking lisinopril/hydrochlorothiazide.

Warnings and precautions

Consult your doctor or pharmacist before starting to take Prinivil Plus:

• if you have difficulty breathing or swallowing with or without swelling of the face, lips, tongue and/or throat, stop taking this medicine and seek medical attention immediately. It should be noted that in black patients, the risk of these types of reactions to ACE inhibitors is increased.
• if you are taking any of the following medicines, the risk of angioedema (rapid swelling under the skin in areas such as the throat) is increased:
• Temsirolimus, sirolimus, everolimus and other medicines of the mTOR inhibitor class (used to prevent organ transplant rejection).
• if you have recently suffered from excessive vomiting or diarrhea.
• if you have a narrowing of the aorta (aortic stenosis), the arteries of the kidneys (renal artery stenosis), or the heart valves (mitral valve stenosis), or an increase in the thickness of the heart muscle (hypertrophic cardiomyopathy).

• if you have kidney problems or are on dialysis.
• if you have liver problems (liver function disorders).
• if you have a disease of the blood vessels (collagen vascular disease) and/or are being treated with allopurinol (for the treatment of gout), procainamide (for heart rhythm disorders), immunosuppressants (medicines that suppress the body's immune response), as you may be at risk of serious infections. In these cases, inform your doctor of any signs of infection.
• if you have diabetes and are taking oral antidiabetics or insulin. Lisinopril/hydrochlorothiazide may increase the risk of hypoglycemia (low blood sugar levels), so you will need to have your glucose levels checked more frequently, especially during the first month of treatment with this medicine. It may be necessary to adjust the dose of your diabetes medicines.
• if you are on a low-salt diet, take potassium supplements or salt substitutes that contain potassium, take potassium-sparing diuretics (medicines that increase urine production), have diabetes or any kidney problems, as they may cause increases in blood potassium levels that can be serious. In these cases, your doctor may need to adjust the dose of Prinivil Plus or check your potassium levels in the blood.
• if you have a cough, as it may be due to treatment.
• if you have gout or high cholesterol levels.
• if you are going to undergo a treatment called low-density lipoprotein (LDL) apheresis.
• if you are going to undergo desensitization treatment to reduce the effect of a bee or wasp sting allergy.
• if you have had skin cancer or if you develop an unexpected skin lesion during treatment. Treatment with hydrochlorothiazide, in particular its long-term use at high doses, may increase the risk of certain types of skin cancer and lip cancer (non-melanoma skin cancer). Protect your skin from sun and UV exposure while taking Prinivil Plus.
• if you experience a decrease in vision or eye pain, they could be symptoms of fluid accumulation in the vascular layer of the eye (choroidal effusion) or an increase in eye pressure and can occur within a few hours to a week after taking Prinivil Plus.

Tell your doctor if you are taking any of the following medicines used to treat high blood pressure (hypertension):

• An angiotensin II receptor antagonist (ARA) also known as a "sartan" - for example, valsartan, telmisartan, irbesartan), especially if you have diabetes-related kidney problems.
• Aliskiren.
• If you are taking a medicine that contains a neprilysin inhibitor (e.g. sacubitril or sacubitril/valsartan). Prinivil Plus should not be administered within 36 hours before or after taking sacubitril/valsartan.

Your doctor may check your kidney function, blood pressure, and blood electrolyte levels (e.g. potassium) at regular intervals.

See also the information under the heading "Do not take Prinivil Plus".

Taking lisinopril/hydrochlorothiazide, especially in the first doses, may cause a sudden drop in blood pressure (you may notice it as dizziness or lightheadedness when standing up. In these cases, lying down may help).

Before undergoing surgery with general or local anesthesia (even at the dentist), inform your doctor or dentist that you are taking this medicine, as a sudden drop in blood pressure may occur in association with anesthesia.

You should inform your doctor if you think you are pregnant (or might be). Lisinopril/hydrochlorothiazide is not recommended during pregnancy and should not be used if you are more than 3 months pregnant, as it may cause serious harm to your baby if used during this period (see section Pregnancy).

Consult your doctor, even if any of the above circumstances have occurred to you in the past.

Children

The safety and efficacy of Prinivil Plus in children have not been established.

Other medicines and Prinivil Plus

Tell your doctor or pharmacist if you are using or have recently used any other medicines, including those obtained without a prescription.

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

• Diuretics (medicines that increase urine production).
• Potassium supplements (including salt substitutes), potassium-sparing diuretics ("water pills") and other medicines that may increase the amount of potassium in the blood (e.g. trimethoprim and cotrimoxazole for bacterial infections; cyclosporin, an immunosuppressant used to prevent organ transplant rejection; and heparin, a medicine used to thin the blood to prevent clots).
• Medicines for mental disorders such as lithium, antipsychotics or tricyclic antidepressants.
• Medicines for the treatment of arthritis or muscle pain, such as gold salts and non-steroidal anti-inflammatory drugs (NSAIDs), including indomethacin and high doses of aspirin (more than 3 grams per day).
• Other antihypertensives (medicines that lower high blood pressure).
• If you are taking an angiotensin II receptor antagonist (ARA) or aliskiren (see also the information under the headings "Do not take Prinivil Plus" and "Prinivil Plus precautions").
• Sympathomimetic medicines (which stimulate the central nervous system).
• Medicines for the treatment of diabetes, such as insulin or oral antidiabetics.
• Medicines commonly used to prevent organ transplant rejection (temsirolimus, sirolimus, everolimus and other medicines of the mTOR inhibitor class). See section "Warnings and precautions".
• Medicines that contain a neprilysin inhibitor (e.g. sacubitril).

Pregnancy and breastfeeding

Consult your doctor or pharmacist before taking any medicine.

Pregnancy

Prinivil Plus is not recommended during pregnancy.

You should inform your doctor if you think you are pregnant (or might be). Normally, your doctor will advise you to stop taking Prinivil Plus before you become pregnant or as soon as you know you are pregnant and will switch you to a different medicine. Prinivil Plus is not recommended at the beginning of pregnancy and should not be taken, in any case, if you are more than 3 months pregnant, as it may cause serious harm to your baby if used from the third month of pregnancy.

Breastfeeding

Tell your doctor if you are breastfeeding or about to start breastfeeding your child. Prinivil Plus is not recommended in breastfeeding mothers and, if you want to breastfeed, your doctor may choose a different treatment, especially if your baby is newborn or premature.

Driving and using machines

Reactions to the medicine may vary from person to person. Certain side effects have been reported with lisinopril/hydrochlorothiazide that may affect the ability to drive or use machines in some patients. If you notice symptoms of dizziness or fatigue, avoid performing tasks that require special attention until you know how you tolerate the medicine (see 4. Possible side effects).

Use in athletes

Athletes are informed that this medicine contains a component (hydrochlorothiazide) that may result in a positive doping control test.

3. How to take Prinivil Plus

Follow exactly the administration instructions of this medicine given by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again. Remember to take your medicine. The doctor will decide the suitable dose, according to the patient's condition and whether or not they are taking other medicines.

The recommended dose is one tablet once a day by mouth, with or without food. Most people take this medicine with water.

If you think the effect of this medicine is too strong or too weak, tell your doctor or pharmacist.

Take this medicine daily, following exactly the doctor's instructions. It is very important to continue taking it for the entire time recommended by the doctor.

Do not take more tablets than the prescribed dose.

If you take more Prinivil Plus than you should

If you have taken more Prinivil Plus than you should, consult your doctor or pharmacist immediately.

The most likely symptoms will be dizziness or lightheadedness due to low blood pressure and/or excessive thirst, confusion, reduced urine production, or rapid heartbeat.

In case of overdose or accidental ingestion, consult the Toxicology Information Service. Telephone: 91 562 04 20.

If you forget to take Prinivil Plus

You should take this medicine as prescribed. Do not take a double dose to make up for forgotten doses. Continue with the normal prescribed plan.

If you stop taking Prinivil Plus

Do not stop taking this medicine even if you feel well, unless your doctor tells you to.

Your doctor will indicate the duration of your treatment with Prinivil Plus. Do not stop treatment before.

If you have any other doubts about the use of this medicine, ask your doctor or pharmacist.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

If you experience any of the following effects, stop taking this medicine and go to the doctor immediately in any of the following cases:

• if you notice swelling of the face, lips, tongue and/or throat that makes it difficult to breathe or swallow
• if you notice swelling of the hands, feet or ankles
• if you develop hives.

It should be noted that in black patients, the risk of these types of reactions to ACE inhibitors is increased.

The initial dose may cause a drop in blood pressure greater than that experienced with continued treatment. The symptoms will be dizziness and dizziness. In this case, it is best to lie down. If it causes you concern, consult your doctor.

The adverse effects observed are limited to those previously reported with lisinopril or hydrochlorothiazide.

Adverse effects of medicines are classified as follows:

Very common: can affect more than 1 in 10 people.

Common:can affect up to 1 in 10 people.

Uncommon: can affect up to 1 in 100 people.

Rare:can affect up to 1 in 1,000 people.

Very rare:can affect up to 1 in 10,000 people.

Frequency not known:cannot be estimated from available data.

Common(can affect up to 1 in 10 people)

• feeling of dizziness or dizziness, especially when standing up quickly
• diarrhea
• vomiting
• cough
• dizziness
• headache.

Uncommon(can affect up to 1 in 100 people)

• rapid and irregular heartbeat
• tingling sensation in certain limbs
• skin rash
• nausea
• inability to obtain an erection (impotence)
• fatigue
• weakness and feeling of weakness.

Rare(can affect up to 1 in 1,000 people)

• dry mouth.

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

• inflammation of the pancreas.

Frequency not known(cannot be estimated from available data)

• muscle cramps or weakness
• gout
• chest pain.

Additional adverse effects reported for individual components that could be potential adverse effects of this medicine are:

HYDROCHLOROTHIAZIDE

Frequency not known(cannot be estimated from available data)

• decrease in blood cell count
• decrease in red blood cells due to premature destruction
• low levels of white blood cells
• decrease in the number of a certain type of white blood cells (neutrophils)
• decrease in platelet count
• low platelet count, sometimes with bleeding or bruising under the skin
• damage to blood vessels that can cause red or purple spots on the skin
• allergic reactions
• severe skin reaction that develops rapidly, causing blisters and peeling of the skin, and possibly ulcers in the mouth
• kidney failure
• kidney function alteration
• kidney inflammation
• yellowing of the skin or the white part of the eyes
• photosensitivity reactions
• skin rash
• respiratory disorders, including pneumonia and fluid accumulation in the lungs
• inflammation of the salivary glands
• yellow vision of objects
• blurred vision
• decreased 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].
• electrolyte imbalance in the blood (including low sodium levels)
• high levels of uric acid in the blood
• high levels of glucose in the blood and/or urine
• loss of appetite
• stomach irritation
• constipation
• vertigo
• fever
• muscle spasms
• fatigue.
• skin and lip cancer (non-melanoma skin cancer).

LISINOPRIL

Common(can affect up to 1 in 10 people)

• kidney function alteration.

Uncommon(can affect up to 1 in 100 people)

• myocardial infarction or stroke, possibly secondary to excessive decrease in blood pressure in high-risk patients
• rapid or unusual heartbeat
• stomach pain
• skin itching
• mood changes.

Rare(can affect up to 1 in 1,000 people)

• acute kidney failure
• increase in blood urea levels
• skin rash
• hair loss
• mental confusion.

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

• decrease in the body's ability to form blood cells, manifested as
• decrease in red blood cell count, platelets and/or white blood cells
• excessive release of antidiuretic hormone (leading to symptoms such as weakness, fatigue, and confusion)
• liver inflammation
• yellowing of the skin and the white part of the eyes
• pseudolymphomatous cutaneous reaction
• breathing difficulties
• decrease in urine output or inability to urinate
• increased sweating.
• Acute respiratory distress (signs include severe respiratory distress, fever, weakness, and confusion).

Reporting of Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that does not appear in this prospectus. You can also report it directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaRAM.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Conservation of Prinivil Plus

Keep this medicine out of sight and reach of children.

This medicine does not require special storage conditions.

Keep in the original package.

Do not use this medicine after the expiration date that appears on the package after CAD. The expiration date is the last day of the month indicated.

Medicines should not be thrown away through the sewers or in the trash. Deposit the packages and medicines you no longer need in the SIGRE Point of the pharmacy. In case of doubt, ask your pharmacist how to dispose of the packages and medicines you no longer need. This way, you will help protect the environment.

6. Package Contents and Additional Information

Composition of Prinivil Plus

• The active ingredients are lisinopril (as dihydrate) and hydrochlorothiazide.

Each tablet contains 20 mg of lisinopril (as dihydrate) and 12.5 mg of hydrochlorothiazide.

• The other components are: mannitol (E-421), calcium hydrogen phosphate dihydrate, corn starch, pregelatinized corn starch, magnesium stearate, and yellow iron oxide (E-172).

Appearance of the Product and Package Contents

Yellow, hexagonal tablet, scored on one side. Prinivil Plus is presented in packages of 28 tablets.

Prinivil Plus contains two different active ingredients.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

PAN QUÍMICA-FARMACÉUTICA, S.A.

Rufino González, 50

28037 Madrid

Spain

Manufacturer

ROVI Pharma Industrial Services, S.A.

Vía Complutense, 140

Alcalá de Henares 28805 – Madrid

(Spain)

Local Representative

Laboratorios Farmacéuticos ROVI, S.A.

Julián Camarillo, 35

28037 Madrid

Spain

Date of Last Revision of this Prospectus:February 2022

The updated and detailed information of this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es