Benazepril and hydrochlorothiazide EG: detailed information

Patient Information Leaflet: Information for the User

BENAZEPRIL HYDROCHLOROTHIAZIDE EG 10 mg/12.5 mg film-coated tablets

Benazepril hydrochloride/Hydrochlorothiazide
Generic medicine
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 their symptoms are the same as yours, as it may be harmful.
If you experience any adverse reactions, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What Benazepril Hydrochlorothiazide EG is and what it is used for

What is Benazepril Hydrochlorothiazide EG?
Benazepril Hydrochlorothiazide EG is a combination of the angiotensin-converting enzyme (ACE) inhibitor benazepril hydrochloride and the thiazide diuretic hydrochlorothiazide. Benazepril hydrochloride belongs to a group of medicines known as angiotensin-converting enzyme inhibitors, which specifically inhibit the conversion of a substance produced by the body called Angiotensin I into a vasoconstrictive substance called Angiotensin II. ACE inhibitors reduce blood pressure in the blood vessels. Thiazide diuretics such as hydrochlorothiazide belong to a group of medicines that promote urinary excretion (diuretics). Like other diuretics in this group, they primarily increase the excretion of electrolytes and secondarily increase urine flow through osmotic water excretion. In patients with essential hypertension, hydrochlorothiazide reduces blood pressure and enhances the effect of other antihypertensive substances.

What Benazepril Hydrochlorothiazide EG is used for:
High blood pressure not caused by organic disease (essential hypertension), when treatment with a combination of medicines is indicated.

The fixed-dose combination of benazepril and hydrochlorothiazide is not intended for initiating treatment or adjusting dosage, but rather to replace the free combination of 10 mg benazepril hydrochloride and 12.5 mg hydrochlorothiazide for maintenance therapy.

2. What you should know before taking Benazepril Hydrochlorothiazide EG

Do not take Benazepril Hydrochlorothiazide EG:

if you are allergic to benazepril hydrochloride, thiazides, or sulfonamides (cross-reactivity may occur), or to any of the other ingredients of this medicine (listed in section 6);
if you are allergic to any other ACE inhibitor, e.g. ramipril;
if you have a tendency to tissue swelling (angioneurotic edema or other forms of angioedema, for example due to previous treatment with ACE inhibitors);
if you are unable to produce urine;
if you suffer from severe renal impairment (serum creatinine above 1.8 mg/dl or creatinine clearance below 30 ml/min);
if you are undergoing dialysis;
if you suffer from narrowing of the renal arteries (bilateral or in a single kidney);
if you have undergone kidney transplantation;
if you suffer from aortic or mitral valve insufficiency or obstructions to outflow from the left ventricle (e.g. hypertrophic cardiomyopathy);
if you have untreated heart muscle weakness (decompensated heart failure);
if you have primary hyperaldosteronism;
if you suffer from primary liver disease or hepatic dysfunction;
if you have a severe disturbance in fluid and electrolyte balance (hypercalcemia, hyponatremia, hypokalemia);
if you have high levels of uric acid in the blood (gout);
in children;
if you are more than three months pregnant. (Benazepril Hydrochlorothiazide EG should also be avoided during early pregnancy – see section Pregnancy);
if you have diabetes or impaired kidney function and are being treated with a blood pressure-lowering medicine containing aliskiren.

Patients being treated with Benazepril Hydrochlorothiazide EG must not undergo dialysis
or hemofiltration using high-flux poly(acrylonitrile, 2-sodium methallyl sulfonate) membranes (e.g. "AN69")
due to the risk of hypersensitivity reactions (anaphylactoid reactions) that may lead to fatal shock.
In case of emergency dialysis or hemofiltration, treatment should be switched to other drugs that
are not ACE inhibitors for the treatment of high blood pressure (hypertension), or a different type of dialysis membrane should be used.
To allow your doctor to make appropriate decisions, inform them if you are being treated with
Benazepril Hydrochlorothiazide EG or if you are scheduled for dialysis.
During low-density lipoprotein (LDL) apheresis (in cases of severe hypercholesterolemia) using
dextran sulfate, life-threatening hypersensitivity reactions may occur when concomitantly treated
with ACE inhibitors.
Life-threatening anaphylactic reactions (e.g. drop in blood pressure, dyspnea, vomiting, skin allergic reactions)
may also occur during concomitant administration of ACE inhibitors and insect venom desensitization therapy (e.g. bee or wasp stings).
If LDL apheresis or insect venom desensitization therapy is required, the ACE inhibitor should be temporarily replaced with other antihypertensive drugs.

Warnings and precautions
Talk to your doctor before taking Benazepril Hydrochlorothiazide EG if any of the following apply to you:

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), especially 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 section “Do not take Benazepril Hydrochlorothiazide EG”;
excessive fluid loss due to: diuretics (medicines that increase urine production); dialysis; low-salt diet; vomiting or diarrhea. At the beginning of treatment, you may experience a significant drop in blood pressure, fainting, or dizziness.
heart problems other than the one being treated. These include valvular disorders, narrowing of blood vessels, or thickening of the heart muscle;
liver or kidney disorders or narrowing of blood vessels leading to the kidney. You must not take this medicine if you have severe kidney or liver problems. See also section “Do not take Benazepril Hydrochlorothiazide EG”;
if you are scheduled for any of the following treatments: o dialysis with high-flux membranes; o cholesterol removal by dialysis-like methods; or o therapies aimed at reducing allergic tendencies. Inform your doctor that you are taking Benazepril Hydrochlorothiazide EG. They may wish to change your treatment to prevent possible allergic reactions.
history of allergy;
if you suffer from a disease causing the immune system to attack the skin and internal organs (systemic lupus erythematosus);
if you are scheduled for surgery under general anesthesia. Inform your doctor that you are taking Benazepril Hydrochlorothiazide EG;
diabetes. It may be necessary to adjust the dose of your antidiabetic medicine;
if you suffer from disorders of fat absorption, metabolism, and/or conversion;
if you experience vision changes or eye pain in one or both eyes while taking Benazepril Hydrochlorothiazide EG. This could be a sign of glaucoma or increased intraocular pressure. Stop treatment with Benazepril Hydrochlorothiazide EG and contact your doctor immediately;
if you are taking any of the following medicines, the risk of angioedema (rapid swelling under the skin, e.g. in the throat) is increased: sirolimus, everolimus, and other drugs belonging to the class of mTOR inhibitors (used to prevent organ transplant rejection).
if you have previously had skin cancer or develop an unexpected skin lesion during treatment. Treatment with hydrochlorothiazide, particularly long-term use at high doses, may increase the risk of certain types of non-melanoma skin cancer and lip cancer. Protect your skin from sun exposure and UV radiation while taking Benazepril Hydrochlorothiazide EG.

Your doctor will regularly monitor your kidney function, electrolyte and blood sugar levels, and blood counts. This will be done more frequently if you have kidney disease, diabetes, or a skin condition.
Inform your doctor if you think you may be pregnant (or if there is a possibility of becoming pregnant). Benazepril Hydrochlorothiazide EG is not recommended during early pregnancy and must not be taken after the third month of pregnancy, as it may cause serious harm to the fetus (see section Pregnancy).
Benazepril Hydrochlorothiazide EG may be less effective in lowering blood pressure in black patients.

Other medicines and Benazepril Hydrochlorothiazide EG
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
The following interactions have been reported with benazepril, ACE inhibitors, or hydrochlorothiazide during concomitant use:

Salt: reduces the antihypertensive effect of Benazepril Hydrochlorothiazide EG.
Antihypertensive medicines, nitrates, vasodilators, barbiturates, phenothiazines, tricyclic antidepressants: increased antihypertensive effect of Benazepril Hydrochlorothiazide EG.
Painkillers and anti-inflammatory medicines (e.g. salicylic acid derivatives, indomethacin): possible weakening of the antihypertensive effect of Benazepril Hydrochlorothiazide EG. Acute renal failure may occur in case of reduced blood volume.
High-dose salicylates: hydrochlorothiazide increases the central nervous system toxicity of salicylates.
Potassium, potassium-sparing diuretics (e.g. spironolactone, amiloride, triamterene), and other medicines that increase serum potassium levels (e.g. heparin): the ACE inhibitor in this medicine increases serum potassium concentrations.
Medicines that increase blood potassium levels (e.g. potassium-sparing diuretics, potassium supplements or potassium-containing salt substitutes, ACE inhibitors, heparin, cyclosporine, non-steroidal anti-inflammatory agents, and cotrimoxazole, also known as trimethoprim/sulfamethoxazole): when used together with Benazepril Hydrochlorothiazide EG, your doctor must regularly monitor blood potassium levels.
Lithium (a medicine used to treat depression): increased serum lithium levels (regular monitoring required!).
Alcohol/medicines containing alcohol: increased blood pressure lowering effect and enhanced effect of alcohol.
Digitalis glycosides (some medicines for heart failure): digitalis glycosides may cause cardiac arrhythmias in case of low potassium and/or magnesium levels.
Oral hypoglycemic agents (e.g. sulfonylureas/biguanides), insulin: hydrochlorothiazide reduces their effects, while benazepril hydrochloride enhances the hypoglycemic effect. Your doctor may need to adjust the dose of these medicines.
Gold used to treat rheumatoid arthritis.
Kaliuretic diuretics (e.g. furosemide), glucocorticoids, ACTH (adrenocorticotropic hormone: used to control adrenal gland function), carbenoxolone (used to treat ulcers and esophagitis), amphotericin B (used to treat fungal infections), penicillin G, salicylates, or laxative abuse: hydrochlorothiazide increases potassium and/or magnesium loss.
Allopurinol, immunosuppressive agents (cytostatic agents, immunosuppressants, systemic corticosteroids, procainamide): decreased white blood cell count (leucopenia).
Medicines that inhibit cell division (cytostatics such as cyclophosphamide, fluorouracil, methotrexate): hydrochlorothiazide potentiates the bone marrow toxicity (especially granulocytopenia).
Sedatives, anesthetics: increased drop in blood pressure (the anesthesiologist must be informed of treatment with Benazepril Hydrochlorothiazide EG).
Cholestyramine or colestipol (medicines used to reduce blood fat levels. If used together, they should be taken several hours apart): reduced absorption of hydrochlorothiazide.
Curare-type muscle relaxants: hydrochlorothiazide potentiates and prolongs the muscle-relaxing effect (the anesthesiologist must be informed of treatment with Benazepril Hydrochlorothiazide EG).
Methyldopa (a medicine for high blood pressure): hemolysis (due to antibody formation against hydrochlorothiazide) in isolated cases.
Allopurinol and amantadine: o allopurinol: a medicine for gout; o amantadine: a medicine for influenza, Parkinson’s disease, or similar disorders. Hydrochlorothiazide may increase the risk of hypersensitivity reactions to allopurinol and adverse reactions to amantadine.
Medicines for gout: hydrochlorothiazide may increase blood uric acid levels. Dose adjustment of anti-gout medicines may be needed.
Diazoxide (a medicine to increase blood sugar): possible increase in blood glucose induced by hydrochlorothiazide.
Vitamin D, calcium salts: increased serum calcium levels induced by hydrochlorothiazide.
Cyclosporine (a medicine used to prevent and treat transplant rejection, severe skin diseases, or severe eye or joint inflammation): increased serum uric acid levels induced by hydrochlorothiazide.
Medicines acting against acetylcholine, a substance produced by the body. These are used for various disorders such as abdominal cramps, muscle and bladder spasms, motion sickness, Parkinson’s disease, and anesthesia preparation (e.g. atropine, biperiden).
Carbamazepine (mainly used for epilepsy and bipolar disorder).
Drugs usually used to prevent organ transplant rejection (sirolimus, everolimus, and other mTOR inhibitors). See section “Warnings and precautions”.

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 sections “Do not take Benazepril Hydrochlorothiazide EG” and “Warnings and precautions”).

Benazepril Hydrochlorothiazide EG with food, drinks, and alcohol

Salt: reduces the antihypertensive effect of Benazepril Hydrochlorothiazide EG.
Alcohol: increases the antihypertensive effect of Benazepril Hydrochlorothiazide EG and the effect of alcohol.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor or pharmacist before taking this medicine.

Pregnancy
You must inform your doctor if you think you may be pregnant (or could become pregnant). Your doctor will normally advise you to stop taking Benazepril Hydrochlorothiazide EG before becoming pregnant or as soon as pregnancy is confirmed, and will recommend an alternative medicine. Benazepril Hydrochlorothiazide EG is not recommended during pregnancy and must not be taken after the third month of pregnancy, as it may cause serious harm to the fetus if taken beyond the third month of pregnancy.

Breastfeeding
Inform your doctor if you are breastfeeding or about to start breastfeeding. Benazepril Hydrochlorothiazide EG is not recommended for women who are breastfeeding.

Driving and using machines
Individual adverse reactions may affect your reaction ability. This may impair your ability to drive or operate machinery or work without secure support. This is particularly important at the beginning of treatment, during dose escalation, when switching to another medicine, and when combined with alcohol.

Benazepril Hydrochlorothiazide EG contains lactose and sodium
If you have been diagnosed with an intolerance to certain sugars, consult your doctor before taking this medicine.
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e. essentially ‘sodium-free’.

3. How to take Benazepril Hydrochlorothiazide EG

Take this medicine exactly as prescribed by your doctor. If you have any doubts, consult your doctor or pharmacist.
The following information applies unless your doctor has prescribed Benazepril Hydrochlorothiazide EG differently. Follow the instructions for use carefully; otherwise, Benazepril Hydrochlorothiazide EG may not work properly.
Generally, treatment of high blood pressure should be initiated with low doses of single active substances, gradually increasing the dose as needed.
The fixed-dose combination Benazepril Hydrochlorothiazide EG containing 10 mg of benazepril hydrochloride and 12.5 mg of hydrochlorothiazide should only be used after prior treatment with benazepril hydrochloride and hydrochlorothiazide administered separately, when the maintenance doses of the individual active substances correspond to those in the fixed combination and adequate blood pressure control has been achieved. If there is no response to therapy, do not increase the dose of this combined medicine. In such cases, continue treatment, for example, by administering the individual components in an appropriate dosing ratio. Due to the possibility of excessive blood pressure drop following an increase in benazepril hydrochloride dosage—especially in patients with salt and/or fluid depletion (e.g., caused by vomiting/diarrhea or previous diuretic treatment) or with severe hypertension—patients must be monitored for at least 6 hours. Correct any salt and/or fluid depletion before starting treatment with Benazepril Hydrochlorothiazide EG. The appropriate dose must be determined by the doctor.
Unless otherwise prescribed by the doctor, the recommended dose is:
The usual dose for patients requiring combination therapy is 1 film-coated tablet of Benazepril Hydrochlorothiazide EG per day. The dose should be adjusted according to the individual needs of the patient. If this combination does not provide adequate blood pressure reduction, administration of 2 film-coated tablets of Benazepril Hydrochlorothiazide EG per day may be considered, following gradual dose escalation of the individual components. In isolated cases of treatment-resistant hypertension, administration of 2 film-coated tablets of Benazepril Hydrochlorothiazide EG twice daily, in the morning and evening, may be justified. Increases in individual doses should occur at intervals of no less than 3 to 4 weeks.
Dosage in case of moderate renal impairment (creatinine clearance 30–60 ml/min or serum creatinine concentrations greater than 1.2 and less than 1.8 mg/dl) and in elderly patients (over 65 years)
Adjust dosage with particular caution (titrate the individual components carefully).
Method of administration
Benazepril Hydrochlorothiazide EG may be taken independently of meals. The daily dose should be taken with sufficient fluid in the morning (e.g., with a glass of water).
Film-coated tablets must not be divided.
Duration of treatment
The duration of treatment will be determined by the doctor.
If you take more Benazepril Hydrochlorothiazide EG than you should
Contact your doctor immediately; they will decide which further measures are necessary.
Symptoms of overdose include:

sudden drop in blood pressure;
fluid and electrolyte imbalance;
cardiac rhythm disturbances;
muscle cramps;
dizziness;
nausea;
drowsiness.

If you forget to take Benazepril Hydrochlorothiazide EG
If you miss a dose, take the next dose at the usual time. Do not take a double dose to make up for the missed dose.
If you have any doubts, consult your doctor.
If you stop taking Benazepril Hydrochlorothiazide EG
In this case, blood pressure may rise again.
If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The side effects listed below refer to Benazepril Hydrochlorothiazide EG and to the drug classes of both active substances.
Stop taking Benazepril Hydrochlorothiazide EG and contact your doctor immediately or go to the nearest hospital emergency department if you experience any of the following serious side effects:

skin rash, itching, swelling of the extremities, face, lips, mouth or throat which may cause difficulty in swallowing or breathing (angioedema).

Side effects may occur with the following frequencies:
Common (may affect up to 1 in 10 people)

palpitations;
drop in blood pressure when standing up quickly, causing dizziness and confusion;
gastrointestinal and intestinal disturbances;
skin rash;
flushing (e.g. of the face);
itching;
increased sensitivity to light;
frequent urination;
cough;
breathing difficulties;
headache;
dizziness;
fatigue;
urticaria and other forms of skin rash;
loss of appetite;
mild nausea;
impotence;
vomiting.

Uncommon (may affect up to 1 in 100 people)

severe decrease in kidney function (signs of acute renal failure).

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

low blood pressure;
chest pain;
diarrhoea;
constipation;
nausea;
abdominal pain;
low potassium levels in the blood;
increased blood urea levels;
increased serum creatinine concentrations, a breakdown product from muscle tissue;
increased blood uric acid concentrations;
drowsiness;
insomnia;
nervousness;
feeling faint;
anxiety;
abnormal sensations such as tingling, prickling, and itching in arms or legs;
joint pain or inflammation;
muscle pain;
pain in skeletal muscles;
lack of blood and oxygen to the heart muscle due to narrowing of blood vessels;
heart rhythm disorders;
liver inflammation, particularly due to reduced bile drainage;
yellowing of the skin, internal organs and/or whites of the eyes, caused by reduced bile drainage;
severe skin disease with blisters, not caused by any apparent reason;
depression;
visual disturbances, particularly during the first weeks of treatment;
decreased platelet count in the blood, causing bruising and a tendency to bleed;
vomiting;
headache;
irregular heartbeat.

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

low sodium levels in the blood;
tinnitus or ringing in the ears;
loss of taste;
heart attack;
inflammation of the pancreas;
reduced kidney function;
severe skin diseases;
skin rash with fever and blisters;
potentially life-threatening disorder causing the outer layer of skin to die and peel off;
diseases causing the immune system to attack the skin and internal organs;
deficiency of red blood cells due to increased breakdown;
deficiency of white blood cells;
deficiency of certain white blood cells, accompanied by sudden high fever, severe sore throat and mouth ulcers;
bone marrow damage, leading to reduced bone marrow and blood cells;
inflammation of blood vessels with tissue damage;
allergic reactions;
breathing difficulties, including lung inflammation and swelling due to fluid accumulation.

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

low concentrations of red pigment in the blood;
severe reduction in blood cells which may cause weakness, bruising or make infections more likely (aplastic anaemia);
increased pressure inside the eye with symptoms such as eye pain and headache, redness of the eyes, reduced vision, nausea and vomiting (possible signs of acute myopia and acute angle-closure secondary glaucoma);
skin rash with red spots (erythema multiforme);
muscle cramps;
kidney problems, even severe ones (renal failure);
fever (pyrexia);
weakness (asthenia);
skin and lip cancer (non-melanoma skin cancer).

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 https://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 Benazepril Hydrochlorothiazide EG

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and blister.
Store below 25°C.

6. Package contents and other information

What Benazepril Hydrochlorothiazide EG contains
The active substances are benazepril hydrochloride and hydrochlorothiazide.
Each film-coated tablet contains 10 mg of benazepril hydrochloride and 12.5 mg of
hydrochlorothiazide.
The other components are:
Tablet core:
Monohydrate lactose, pregelatinized starch, sodium croscarmellose, hydrogenated castor oil.
Coating:
Hypromellose, titanium dioxide (E171), macrogol 8000, talc, iron oxide (III) (E172).
Pack contents
Benazepril Hydrochlorothiazide EG is available in packs containing 10, 14, 20, 28, 30, 42, 50, 98 and 100
film-coated tablets.
Not all pack sizes may be marketed.
Marketing Authorization Holder
EG S.p.A., Via Pavia, 6 - 20136 Milan, Italy
Manufacturers
STADA Arzneimittel AG, Stadastrasse 2-18, 61118 Bad Vilbel, Germany
This medicinal product is authorized in the European Economic Area countries under the
following names:
Italy: Benazepril Hydrochlorothiazide EG
Germany: Benazeplus STADA 10 mg/12.5 mg Film Tablets