Package leaflet: Information for the user

FOSICOMBI 20 mg + 12.5 mg tablets

Fosinopril sodium + hydrochlorothiazide
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 others, even if they have the same symptoms as you, because it could be harmful.
If you experience any side effects, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. WHAT FOSICOMBI IS AND WHAT IT IS USED FOR

FOSICOMBI contains the active substances fosinopril sodium (belonging to the pharmacological class of ACE inhibitors, medicines used to lower blood pressure) and hydrochlorothiazide (a diuretic medicine belonging to the sulfonamides, which increases urine production).
FOSICOMBI is used in adults for the treatment of high blood pressure (arterial hypertension).

2. WHAT YOU NEED TO KNOW BEFORE TAKING FOSICOMBI

Do not take FOSICOMBI

if you are allergic to sodium fosinopril or any other ACE inhibitor; if you are allergic to hydrochlorothiazide or thiazides or to other sulphonamide-derived medicines or to any of the other ingredients of this medicine (listed in section 6);
if you are unable to pass urine (anuria);
if you have previously experienced sudden swelling of the skin, mucous membranes and submucosal tissues (angioedema) associated with prior treatment with ACE inhibitors or of unknown origin (hereditary/idiopathic angioedema);
if you have diabetes mellitus or impaired renal function and are being treated with a blood pressure-lowering medicine containing the active substance aliskiren;
if you are in the second or third trimester of pregnancy (see “Pregnancy, breastfeeding and fertility”).

Warnings and precautions
Talk to your doctor or pharmacist before taking FOSICOMBI.
Talk to your doctor or pharmacist before taking FOSICOMBI 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 – for example, valsartan, telmisartan, irbesartan), particularly if you have kidney problems related to diabetes;
aliskiren (see “Do not take FOSICOMBI”).

Your doctor may check your kidney function, blood pressure and levels of electrolytes (e.g. potassium) in your blood at regular intervals.
See also information under “Do not take FOSICOMBI”.
Talk to your doctor or pharmacist before taking FOSICOMBI also if you are in any of the following situations.
Aortic stenosis
Take FOSICOMBI with caution if you have stenosis (pathological narrowing) of the aorta, as, like any medicine that reduces vascular resistance, it may lead to a dangerous reduction in coronary perfusion (i.e. reduced blood flow to the coronary arteries of the heart) due to decreased blood pressure.
Dual blockade of the renin-angiotensin-aldosterone system (RAAS)
Concomitant use of ACE inhibitors, angiotensin II receptor antagonists (medicines used to treat hypertension) or aliskiren increases the risk of hypotension, hyperkalaemia (increased potassium levels in the blood) and leads to reduced renal function (including acute renal failure). Dual blockade of the RAAS through the combined use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren is therefore not recommended (see “Do not take FOSICOMBI” and “Other medicines and FOSICOMBI”).
If dual RAAS blockade therapy is considered absolutely necessary, it should only be carried out under the supervision of a specialist doctor and with close and frequent monitoring of renal function, electrolytes and blood pressure.
ACE inhibitors and angiotensin II receptor antagonists must not be used simultaneously in patients with diabetic nephropathy (kidney damage due to diabetes).
Anaphylactoid reactions during desensitisation
In patients undergoing desensitisation treatment with hymenoptera venom (e.g. bees, wasps) and who were taking another ACE inhibitor (enalapril, belonging to the same class as fosinopril), prolonged anaphylactoid reactions (severe and sudden allergic-like reactions similar to anaphylaxis, but based more on a toxic than immunological mechanism) have been reported.
Therefore, in such cases, an antihypertensive of a different class should be used.
Impaired liver function
Use thiazide diuretics with caution if you have severe liver dysfunction, as even minor changes in blood volume or serum (plasma) electrolyte concentration may lead to hepatic coma (see “Do not take FOSICOMBI”).
Stop treatment with FOSICOMBI and seek specific medical evaluation if you develop jaundice (yellowing of the skin, sclera and mucous membranes) or show marked increases in liver enzymes during treatment with the medicine.
Rarely, ACE inhibitors have been associated with a syndrome beginning with cholestatic jaundice (jaundice due to impaired bile flow from the liver to the intestine) and progressing to fulminant hepatic necrosis (destruction of liver cells), sometimes with fatal outcome. The mechanism of this syndrome is not fully understood.
Patients with impaired liver function may develop elevated plasma levels of fosinopril. In a study in patients with alcoholic or biliary cirrhosis, total clearance of fosinopril (i.e. the body’s ability to eliminate the drug) was reduced.
Impaired kidney function
FOSICOMBI may be administered to patients with mild or moderate impairment of kidney function (creatinine clearance greater than 30 ml/min).
If you have severe impairment of kidney function (creatinine clearance less than 30 ml/min), the use of FOSICOMBI, due to the presence of the thiazide diuretic, is not recommended.
If you are being treated with fosinopril and a diuretic is also required, your doctor should prefer the use of furosemide (another type of medicine belonging to the diuretic class).
In patients with congestive heart failure associated with renal failure, administration of an ACE inhibitor or a thiazide diuretic may cause excessive hypotension, sometimes associated with oliguria or elevated azotemia, and rarely, acute renal failure and death. In such patients, treatment with FOSICOMBI must be carried out under close medical supervision.
In hypertensive patients with bilateral renal artery stenosis or renal artery stenosis in a single kidney, ACE inhibitor therapy may lead to increased serum creatinine and azotemia. These changes regress upon discontinuation of therapy.
Mild and transient increases in azotemia and serum creatinine may occasionally occur even in patients with apparently normal renovascular function, particularly if concomitantly treated with diuretics.
This occurrence is more frequent in patients with pre-existing renal function impairment and may require dosage reduction.
Diabetes
If you have diabetes, the effects of insulin may be altered by thiazide diuretics. Latent (hidden) diabetes may manifest during treatment with thiazide diuretics.
Surgery/anesthesia
In patients undergoing surgery, the use of FOSICOMBI may increase the hypotensive effect (blood pressure-lowering effect) of anaesthetics and analgesics (painkillers). In such cases, expansion of blood or plasma volume may be required.
During treatment with FOSICOMBI, the following may occur:
Hypotension and disturbances in fluid and electrolyte balance
Like other ACE inhibitors, FOSICOMBI may cause hypotension, especially if you are receiving concomitant antihypertensive therapy or if you have volume and/or sodium depletion due to intensive diuretic therapy, dietary salt restriction, diarrhoea, vomiting or dialysis. Before starting treatment with FOSICOMBI, your doctor should correct volume (reduction in the amount of water in the body) and/or sodium depletion.
In patients with congestive heart failure (a pathological condition caused by the heart’s inability to pump adequate blood to meet the body’s needs), whether or not associated with renal dysfunction, ACE inhibitors may cause excessive hypotension, sometimes associated with hyperazotemia (increased nitrogen levels in the blood) or oliguria (reduced urine output), leading to acute renal failure, potentially fatal. In such cases, treatment should be initiated under careful medical supervision, preferably in a hospital setting; patients should be closely monitored, especially during the first 2 weeks of treatment and when doses are increased.
If you are being treated with diuretics (such as hydrochlorothiazide, contained in FOSICOMBI), you should be medically monitored for possible symptoms of fluid-electrolyte imbalance, such as dryness of the mouth (area between mouth and pharynx), thirst, weakness, lethargy, drowsiness, agitation, muscle pain or cramps, fatigue, hypotension, oliguria, tachycardia (increased heart rate) and gastrointestinal disturbances such as nausea or vomiting; however, since fosinopril reduces aldosterone production, its combination with hydrochlorothiazide may minimise or eliminate the potential incidence of diuretic-induced hypokalaemia.
Chloride deficiency is generally mild and usually does not require treatment.
Thiazide diuretics may decrease urinary calcium excretion and cause intermittent and mild increases in blood calcium levels in the absence of confirmed disorders of calcium metabolism. Marked hypercalcaemia may indicate underlying hyperparathyroidism (increased parathyroid function). Discontinue thiazide treatment before performing tests for parathyroid function, as thiazides increase urinary magnesium excretion, which may result in hypomagnesaemia (decreased magnesium levels in the blood).
Thiazides may enhance the effect of antihypertensive medicines, thereby increasing the hypotensive effect, and may in turn be potentiated if the patient has undergone sympathectomy (surgical interruption of sympathetic nerve pathways performed to treat certain conditions).
Angioedema of the head and neck
Immediately stop treatment with FOSICOMBI and seek appropriate treatment if you develop angioedema (sudden swelling of the skin, mucous membranes and submucosal tissues); your doctor will keep you under close observation until the clinical condition resolves completely.
During treatment with fosinopril, angioedema may occur in the extremities, face, lips, mucous membranes, tongue, glottis or larynx. Angioedema involving the tongue, glottis or larynx may cause airway obstruction and be fatal. In such cases, emergency treatment must be administered, including subcutaneous injection of a 1:1000 adrenaline solution (0.3–0.5 ml); the patient must be hospitalised and observed for at least 12 to 24 hours and must not be discharged before symptoms have completely resolved.
Intestinal angioedema
Intestinal angioedema has been rarely reported in patients treated with ACE inhibitors, presenting with abdominal pain (with or without nausea or vomiting); in some cases, there was no history of facial angioedema and C-1 esterase levels (a parameter for diagnosing hereditary angioedema) were normal. Intestinal angioedema may be diagnosed by abdominal CT scan or ultrasound, or during surgery, and symptoms may resolve after discontinuation of the ACE inhibitor. Intestinal angioedema should be included in the differential diagnosis of patients treated with ACE inhibitors who present with abdominal pain.
Cough
A non-productive (dry) cough has been reported with the use of ACE inhibitors, including fosinopril, which resolves upon discontinuation of treatment (see section 4 “Possible side effects”). In the differential diagnosis of cough, ACE inhibitor-induced cough should be considered.
Neutropenia/agranulocytosis
Rare cases of agranulocytosis (severe reduction in the number of granulocytes, a type of white blood cell, in the blood) and bone marrow depression (reduced production of blood components in the bone marrow) have been reported in patients taking ACE inhibitors such as captopril, particularly in patients with concomitant renal failure and/or collagen diseases (structural protein component of connective tissue), e.g. Systemic Lupus Erythematosus, scleroderma, or those receiving immunosuppressive medicines (medicines that reduce or block immune response). Available data are insufficient to demonstrate that fosinopril does not cause agranulocytosis. It is advisable to undergo periodic white blood cell monitoring if you have renal failure and/or collagen diseases.
Report any signs of infection (e.g. sore throat, fever) during treatment. In such cases, a white blood cell count should be performed.
Systemic Lupus Erythematosus (SLE)
Worsening of Systemic Lupus Erythematosus (a chronic disease that can affect various organs and tissues of the body, in which the immune system produces responses directed against the body's own components) has been reported following the use of thiazide diuretics.
Anaphylactoid reactions during exposure to high-flux dialysis membranes/lipoprotein apheresis
Anaphylactoid reactions have been reported in haemodialysed patients (undergoing physical therapy replacing kidney function) using high-flux dialysis membranes (i.e. capable of removing medium-sized toxins), undergoing low-density lipoprotein apheresis by dextran-sulphate adsorption (accumulation on a surface coated with a polymer binding lipoproteins). In such patients, consider using different types of dialysis membranes or different classes of antihypertensive medicines.
Metabolic and endocrine effects
Increases in cholesterol and triglyceride (fats) levels have been associated with high-dose thiazide diuretic therapy.
Hyperuricaemia (increased blood uric acid levels) or gout (a metabolic disease characterised by joint inflammation causing pain and swelling due to deposition of uric acid crystals) may occur in some patients treated with thiazide diuretics.
Interactions with laboratory tests
Stop treatment with FOSICOMBI several days before performing parathyroid function tests. Hydrochlorothiazide may interfere with the bentiroamine diagnostic test (a test to assess pancreatic function).
Furthermore, fosinopril may falsely lower the results of blood digoxin level measurements using the Digi-Tab RIA Kit, resulting in digoxin levels lower than actual.
For athletes: using the medicine without therapeutic need constitutes doping and may result in a positive anti-doping test.
Children and adolescents
The safety and efficacy of FOSICOMBI in children have not been established.
Other medicines and FOSICOMBI
Inform your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
Potassium-sparing diuretics or potassium supplements
ACE inhibitors reduce diuretic-induced potassium loss. Potassium-sparing diuretics (spironolactone, triamterene or amiloride) or potassium supplements may lead to increased serum potassium levels (hyperkalaemia). If concomitant use is indicated due to manifest hypokalaemia, they should be used with caution and with frequent monitoring of blood potassium levels (see “Warnings and precautions”).
Other diuretics and antihypertensives
The thiazide component of FOSICOMBI may enhance the action of other antihypertensives, especially adrenergic blockers. Hydrochlorothiazide may interact with diazoxide (a medicine used in hypertensive emergencies and hypoglycaemia). You should therefore be monitored for blood pressure, blood glucose and uric acid levels.
ACE inhibitors, angiotensin II receptor antagonists or aliskiren
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 FOSICOMBI” and “Warnings and precautions”).
Antacids (medicines that neutralise excessive stomach acidity)
Take antacid medicines at least 2 hours apart from FOSICOMBI, as absorption of fosinopril may be affected by aluminium hydroxide, magnesium hydroxide and simethicone.
Antigout medicines
Concomitant use of FOSICOMBI and antigout medicines (medicines used to treat gout, a metabolic disease characterised by joint inflammation causing pain and swelling due to deposition of uric acid crystals) may require dosage adjustment of the latter, as hydrochlorothiazide may increase uric acid levels. An increased dosage of probenecid or sulfinpyrazone may be necessary.
Antidiabetics (oral and insulin)
Taking fosinopril may lead to increased blood glucose levels. In such cases, it may be necessary to reduce the dose of antidiabetic medicine during concomitant treatment with FOSICOMBI.
Calcium salts
During treatment with FOSICOMBI, increased blood calcium concentration may occur due to reduced excretion. If your doctor prescribes calcium supplementation, calcium levels should first be checked and dosage adjusted if necessary.
Cholestyramine and colestipol (medicines that lower blood cholesterol)
These medicines may delay or reduce absorption of hydrochlorothiazide.
Take FOSICOMBI at least 1 hour before or 4 to 6 hours after these medicines.
Medicines used in surgery
The effects of non-depolarising muscle relaxants (used to inhibit muscle contraction during anaesthesia, e.g. tubocurarine chloride), pre-anaesthetics and anaesthetics may be potentiated by hydrochlorothiazide, so dosage adjustments may be required.
Pre-anaesthetics and anaesthetics should be administered in reduced doses and treatment with hydrochlorothiazide should be discontinued one week before surgery. Fluid and electrolyte imbalances should be checked and corrected before surgery, if possible. Caution is required in patients taking FOSICOMBI and pressor agents (e.g. adrenaline) undergoing surgery.
Lithium
Extreme caution is recommended when combining fosinopril and hydrochlorothiazide with lithium.
Increased lithium blood concentrations and lithium toxicity have been reported during concomitant administration of lithium and ACE inhibitors. Concomitant use of thiazide diuretics may increase the risk of lithium toxicity and potentiate the already high risk of lithium toxicity with ACE inhibitors.
Careful monitoring of lithium blood levels should be performed if combination therapy is necessary.
Non-steroidal anti-inflammatory drugs (NSAIDs)
When ACE inhibitors are administered simultaneously with non-steroidal anti-inflammatory drugs (e.g. selective COX-2 inhibitors such as celecoxib or valdecoxib, acetylsalicylic acid at doses ≥ 325 mg/day and non-selective NSAIDs), attenuation of the antihypertensive effect may occur. It has also been reported that indomethacin reduces the antihypertensive efficacy of ACE inhibitors, particularly in patients with low-renin hypertension (renin being an important molecule involved in blood pressure regulation).
Concomitant use of ACE inhibitors and NSAIDs may increase the risk of worsening renal function, including possible acute renal failure and increased potassium levels in the blood, especially in patients with pre-existing impaired renal function.
Use FOSICOMBI with caution, especially if you are elderly. You should be adequately hydrated and monitoring of renal function should be considered at the start of concomitant therapy.
In some patients, NSAIDs may reduce the effects of diuretics such as hydrochlorothiazide.
Barbiturates, narcotics
Concomitant use of barbiturates or narcotics with FOSICOMBI may increase orthostatic hypotension (decreased blood pressure upon changing from lying to standing position) caused by thiazide diuretics.
FOSICOMBI with alcohol
Concomitant use of FOSINOPRIL and alcohol may increase orthostatic hypotension caused by thiazide diuretics.
Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor or pharmacist before taking this medicine.
Pregnancy
FOSINOPRIL
Do not start treatment with FOSICOMBI if you are pregnant.
When pregnancy is diagnosed, treatment with ACE inhibitors must be immediately discontinued and, if appropriate, alternative therapy initiated.
Do not take FOSICOMBI during the second and third trimesters of pregnancy (see “Do not take FOSICOMBI”).
Use of ACE inhibitors is not recommended during the first trimester of pregnancy.
Evidence regarding teratogenic risk (abnormal fetal development during pregnancy) following exposure to ACE inhibitors during the first trimester of pregnancy is inconclusive; however, a small increased risk cannot be excluded.
It is known that exposure to ACE inhibitors during the second and third trimesters of pregnancy causes fetal toxicity (reduced renal function, oligohydramnios, i.e. reduced amniotic fluid volume, delayed skull ossification), neonatal toxicity (renal failure, hypotension, hyperkalaemia, i.e. increased potassium levels in the blood) and fetal death.
If exposure to an ACE inhibitor occurs from the second trimester of pregnancy, an ultrasound assessment of renal and skull development is recommended.
Newborns whose mothers took ACE inhibitors should be closely monitored for hypotension (see “Do not take FOSICOMBI”).
If you are planning a pregnancy, you should use alternative antihypertensive treatments with a proven safety profile in pregnancy, unless continuation of ACE inhibitor therapy is considered essential.
HYDROCHLOROTHIAZIDE
Experience with hydrochlorothiazide during pregnancy is limited, especially during the first trimester. Animal studies are insufficient.
Hydrochlorothiazide crosses the placenta. Based on its mechanism of action, use of hydrochlorothiazide during the second and third trimesters of pregnancy may impair fetoplacental perfusion and may cause fetal and neonatal effects such as jaundice (yellowing of the skin, sclera and mucous membranes), electrolyte imbalance and thrombocytopenia (decreased platelet count).
Do not take hydrochlorothiazide for the treatment of:

gestational oedema (fluid accumulation occurring during pregnancy), gestational hypertension or pre-eclampsia (a serious pregnancy complication affecting both mother and fetus, characterised by oedema, hypertension and proteinuria, i.e. protein loss in urine), due to the risk of reduced blood volume and placental hypoperfusion (reduced blood flow to the placenta) without beneficial effect on disease progression;
hypertension, if you are pregnant, except in rare situations where no other treatment could be used.

Breastfeeding
FOSINOPRIL
Use of FOSICOMBI during breastfeeding is not recommended and alternative treatments with a proven safety profile should be preferred, especially when breastfeeding newborns or premature infants, due to very limited data on the use of fosinopril during breastfeeding.
HYDROCHLOROTHIAZIDE
Use of FOSICOMBI during breastfeeding is not recommended. If FOSICOMBI is taken during breastfeeding, doses should be kept as low as possible.
Hydrochlorothiazide is excreted in breast milk in small amounts. High-dose thiazide diuretics cause intense diuresis which may inhibit milk production.
Driving and use of machines
Although FOSICOMBI does not affect the ability to drive or operate machinery, very rarely side effects such as dizziness and visual disturbances may occur.
FOSICOMBI 20 mg + 12.5 mg tablets contain lactose. If your doctor has diagnosed you with an intolerance to certain sugars, contact him before taking this medicine.

3. HOW TO TAKE FOSICOMBI

Take this medicine exactly as prescribed by your doctor or pharmacist.
If you have any doubts, consult your doctor or pharmacist.

Arterial hypertension
The recommended dose of FOSICOMBI is 1 tablet daily, preferably taken in the morning.
Most patients respond to this dosage regimen; however, if a further reduction in arterial pressure is considered necessary, the daily dose may be doubled.
This dosage regimen is also valid for elderly patients.
FOSICOMBI may also be taken in case of mild or moderate renal impairment (creatinine clearance greater than 30 ml/min).

Use in children and adolescents
The safety and efficacy of FOSICOMBI in children have not been established.

If you take more FOSICOMBI than you should
In case of overdose, contact your doctor immediately or go to the nearest hospital.
No cases of overdose with FOSICOMBI have been reported. Treatment of overdose is symptomatic (aimed at relieving symptoms) and supportive.
Dehydration, electrolyte imbalance, hypotension, and diuretic overdose-induced coma should be treated with standard therapies.
Fosinopril is poorly removed by both hemodialysis and peritoneal dialysis. The extent of hydrochlorothiazide removal by hemodialysis has not been established.

If you forget to take FOSINOPRIL
Do not take a double dose to make up for the missed dose.
If you have any doubts about the use of this medicine, consult your doctor or pharmacist.

4. POSSIBLE ADVERSE REACTIONS

Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them.
The adverse reactions observed most frequently in clinical studies conducted with FOSICOMBI (although not necessarily related to treatment) were: headache, cough, asthenia (loss of strength), dizziness, upper respiratory tract infections, musculoskeletal pain. These were generally mild and transient in nature.

Adverse reactions:

Chest pain, weakness, fever;
Orthostatic hypotension (see "Warnings and precautions"), edema, flushing (reddening), arrhythmias (disturbances in heart rhythm), syncope;
Pruritus, rash (sudden reddening of the skin);
Sexual dysfunction, changes in libido;
Nausea and vomiting, diarrhoea, dyspepsia/heartburn, abdominal pain, gastritis/oesophagitis (inflammation of the stomach or oesophagus);
Angioedema (see "Warnings and precautions");
Myalgia (muscle pain)/muscle cramps;
Somnolence, depression, numbness/paresthesia (altered sensation in limbs or other body parts);
Sinusitis (inflammation of the paranasal sinuses), pharyngitis (inflammation of the pharynx), rhinitis (irritation and inflammation of the nasal mucosa);
Tinnitus (ringing in the ears);
Pollakiuria (frequent passage of small volumes of urine), dysuria (difficulty in passing urine);
Neutropenia;
Changes in levels of electrolytes, uric acid, glucose, magnesium, cholesterol, triglycerides, calcium.
Other adverse reactions observed with fosinopril or hydrochlorothiazide taken separately include:
Angina (chest pain due to insufficient oxygenation of the heart muscle following a temporary reduction in blood flow), myocardial infarction (death of a more or less extensive portion of cardiac muscle tissue due to sudden interruption of blood supply), cerebrovascular accidents, hypotension, claudication (difficulty in walking);
Urticaria (more or less itchy skin rash characterized by the appearance of roundish skin elevations, pinkish or sometimes pale in colour, disappearing more or less rapidly), photosensitivity (excessive reaction to light);
Gout;
Pancreatitis (inflammation of the pancreas), cholestatic jaundice, hepatitis (liver inflammation); aplastic anaemia and haemolytic anaemia (diseases affecting red blood cells), agranulocytosis, leukopenia (reduced level of white blood cells in the blood), thrombocytopenia, lymphadenopathy (enlargement of lymph nodes);
Necrotizing vasculitis (severe inflammation of blood vessels), Stevens-Johnson syndrome (a severe acute hypersensitivity reaction in which the skin and mucous membranes react to a medicine or infection), respiratory disorders (including pneumonia and pulmonary edema), purpura (bleeding under the skin leading to purple-coloured spots);
Arthralgia (joint pain);
Dizziness, sensation of light-headedness, paresthesia;
Bronchospasm (narrowing of the bronchial lumen);
Visual disturbances, dysgeusia (altered sense of taste);
Renal failure;
Increased levels of the following parameters: transaminases, LDH, alkaline phosphatase, and bilirubin.

Reporting of adverse reactions
If you experience any adverse reaction, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report adverse reactions directly via the national reporting system at the following website:
http://www.agenziafarmaco.gov.it/it/responsabili.
By reporting adverse reactions, you can help provide more information on the safety of this medicine.

5. HOW TO STORE FOSICOMBI

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of that month.
Store at room temperature and protect from moisture.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer used. This will help protect the environment.

6. CONTENTS OF THE PACKAGE AND OTHER INFORMATION

What FOSICOMBI contains
FOSICOMBI 20 mg + 12.5 mg tablets
Each tablet contains:
Active substances: Sodium fosinopril 20 mg (equivalent to 19.2 mg of fosinopril) + Hydrochlorothiazide 12.5 mg.
Other components: hydrated lactose, anhydrous lactose, sodium croscarmellose, povidone, sodium stearyl fumarate, red iron oxide, yellow iron oxide.

Description of the appearance of FOSICOMBI and contents of the package
Round, biconvex tablets with a break line on one side, peach-coloured.
Carton containing 14 tablets in blister packs.

Marketing Authorisation Holder
A. Menarini Industrie Farmaceutiche Riunite s.r.l., Via Sette Santi, 3 – Florence.

Manufacturer
A. Menarini Manufacturing Logistics and Services s.r.l., Campo di Pile - L'Aquila.
Menarini Von Heyden GmbH, Leipziger Strasse 7-13, Dresden (Germany).

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