SmPC Fosinopril/HCT DE730 - PRAC recommendations EPITT No 19468 - Choroidal effusion 2020-04-16 SUMMARY OF PRODUCT CHARACTERISTICS 1. NAME OF THE MEDICINAL PRODUCT Fosinopril HCT 2. QUALITATIVE AND QUANTITATIVE COMPOSITION 1 tablet contains 20 mg fosinopril sodium and 12.5 mg hydrochlorothiazide. Excipient with known effect: 221.5 mg lactose monohydrate and up to 1.60 mg sodium per tablet For the full list of excipients, see section 6.1 3. PHARMACEUTICAL FORM Tablet Light orange, round, flat, not film-coated tablets with a diameter of 9 mm and marked “FH” on one side. 4. CLINICAL PARTICULARS 4.1 Therapeutic Indications Treatment of essential hypertension. Fosinopril HCT is indicated for the treatment of essential hypertension in patients who have inadequately responded to the treatment with fosinopril as monotherapy. The fixed dose may also replace the combination of 20 mg fosinopril and 12.5 mg hydrochlorothiazide in patients who have been stabilised on the individual active substances given in the same proportions as separate medications. 4.2 Posology and method of administration Posology The fixed dose combination is not suitable for initial therapy. Individual dose titration with the components is recommended. When clinically appropriate, direct change from monotherapy to the fixed combination may be considered. Adults The usual dose in patients to whom combination therapy is indicated is 1 tablet of Fosinopril HCT once daily. An excessive fall in blood pressure may occur in patients with salt and/or volume depletion (e.g. vomiting / diarrhoea, concomitant treatment with diuretics) accompanying heart failure or severe hypertension. Patients with impaired renal function In severe renal insufficiency (creatinine clearance < 30 ml/min) Fosinopril HCT tablets are contraindicated (see section 4.3). In patients with renal impairment (creatinine clearance > 30 ml/min and < 80 ml/min, serum 1 SmPC Fosinopril/HCT DE730 - PRAC recommendations EPITT No 19468 - Choroidal effusion 2020-04-16 creatinine roughly 3 mg/dL or 265 µmol/L) dose adjustment should be carried out with special care (gradual titration of individual components). Paediatric population The combination of fosinopril and hydrochlorothiazide is not recommended for children and adolescents below 18 years due to lack of data on safety and efficacy. Older people No dosage reduction is necessary in patients with clinically normal renal and hepatic function as no significant differences in the pharmacokinetic parameters or antihypertensive effect have been found compared with younger subjects. Method of administration The medicine may be taken independent of meals. The daily dose should be taken in a single dose in the morning with some liquid. Duration of treatment Treatment with these tablets can be continued without any time limits according to the clinical response, if no side effects occur. The duration of administration is determined by the treating physician. 4.3 Contraindications Fosinopril HCT must not be used in: hypersensitivity to fosinopril sodium, to any other ACE inhibitors or to hydrochlorothiazide or to any other thiazides or sulphonamides (note possible cross-reactions) or to any of the excipients listed in section 6.1 angioneurotic oedema relating to previous treatment with an ACE inhibitor hereditary or idiopathic angioneurotic oedema severe renal impairment (creatinine clearance < 30 ml/min) severe hepatic impairment (precoma/coma hepaticum) patients who are anuric second and third trimesters of pregnancy (see sections 4.4 and 4.6) concomitant use with sacubitril/valsartan therapy. Fosinopril HCT must not be initiated earlier than 36 hours after the last dose of sacubitril/valsartan (see also sections 4.4 and 4.5). The concomitant use of Fosinopril HCT with aliskiren-containing products is contraindicated in patients with diabetes mellitus or renal impairment (GFR < 60 ml/min/1.73 m2) (see sections 4.5 and 5.1). Hypersensitivity reactions are more likely to occur in patients with a history of allergy or bronchial asthma. 4.4 Special warnings and precautions for use Fosinopril sodium Hypersensitivity / angioedema Concomitant use of ACE inhibitors with sacubitril/valsartan is contraindicated due to the increased risk of angioedema. Treatment with sacubitril/valsartan must not be initiated earlier than 36 hours after the last dose of fosinopril. Treatment with fosinopril must not be initiated earlier than 36 hours after the last dose of sacubitril/valsartan (see sections 4.3 and 4.5). Concomitant use of ACE inhibitors with racecadotril, mTOR inhibitors (e.g. sirolimus, everolimus, temsirolimus) and vildagliptin may lead to an increased risk of angioedema (e.g. swelling of the airways or tongue, with or without respiratory impairment) (see section 4.5). 2 SmPC Fosinopril/HCT DE730 - PRAC recommendations EPITT No 19468 - Choroidal effusion 2020-04-16 Caution should be used when starting racecadotril, mTOR inhibitors (e.g. sirolimus, everolimus, temsirolimus) and vildagliptin in a patient already taking an ACE inhibitor. Angioedema of the face, extremities, lips, tongue, glottis and/or larynx has been reported rarely in patients treated with ACE inhibitors, including fosinopril sodium. This may occur at any time during therapy. In such cases, fosinopril sodium should be discontinued promptly and appropriate treatment and monitoring should be instituted to ensure complete resolution of symptoms prior to dismissing the patients. Even in those instances where swelling of only the tongue is involved, without respiratory distress, patients may require prolonged observation since treatment with antihistamines and corticosteroids may not be sufficient. Very rarely, fatalities have been reported due to angioedema associated with laryngeal oedema or tongue oedema. Patients with involvement of the tongue, glottis or larynx are likely to experience airway obstruction, especially those with a history of airway surgery. In such cases emergency therapy should be administered promptly. This may include the administration of adrenaline and/or the maintenance of a patent airway. The patient should be under close medical supervision until the symptoms have completely and permanently disappeared. ACE inhibitors cause a higher incidence of angioedema in black patients than in non-black patients. Patients who have an anamnesis of angioedema that is unrelated to the administration of an ACE inhibitor may have a higher risk of developing angioedema during use of an ACE inhibitor (see section 4.3). Intestinal angioedema Intestinal angioedema has been reported rarely in patients treated with ACE inhibitors. These patients presented with abdominal pain (with or without nausea or vomiting); in some cases there was no prior history of facial angioedema and C -1 esterase levels were normal. The angioedema was diagnosed by procedures including abdominal CT scan or ultrasound, or at surgery, and symptoms resolved after stopping the ACE inhibitor. Intestinal angioedema should be included in the differential diagnosis of patients on ACE inhibitors presenting with abdominal pain. Anaphylactoid reactions in haemodialysis patients Anaphylactoid reactions have been reported in patients dialysed with high flux membranes (e.g. AN 69) and treated concomitantly with an ACE inhibitor. In these patients consideration should be given to using a different type of dialysis membrane or different class of antihypertensive agent. Anaphylactoid reactions during low-density lipoproteins (LDL) apheresis Rarely, patients receiving ACE inhibitors during LDL apheresis with dextran sulphate have experienced life-threatening anaphylactoid reactions. These reactions were avoided by temporarily withholding ACE inhibitor therapy prior to each apheresis. Anaphylactoid reactions during desensitisation Patients receiving ACE inhibitors during desensitisation treatment (e.g. hymenoptera venom) have sustained life-threatening anaphylactoid reactions. In the same patients, these reactions have been avoided when ACE inhibitors were temporarily withheld but they have reappeared upon inadvertent re-administration of the medicinal product. Therefore, caution should be used in patients treated with ACE inhibitors undergoing such desensitisations procedures. Symptomatic hypotension Symptomatic hypotension is observed rarely in uncomplicated hypertensive patients. In hypertensive patients receiving fosinopril sodium, hypotension is more likely to occur if the 3 SmPC Fosinopril/HCT DE730 - PRAC recommendations EPITT No 19468 - Choroidal effusion 2020-04-16 patient has been volume-depleted e.g. by diuretic therapy, dietary salt restriction, dialysis, diarrhoea or vomiting, or has severe renin-dependent hypertension (see section 4.5 and section 4.8). In patients at increased risk of symptomatic hypotension, initiation of therapy and dose adjustment should be closely monitored. Similar considerations apply to patients with ischaemic heart or cerebrovascular disease in whom an excessive fall in blood pressure could result in myocardial infarction or cerebrovascular accident. If hypotension occurs, the patient should be placed in the supine position and, if necessary, should receive an intravenous infusion of sodium chloride 9 mg/ml (0.9 %) solution. A transient hypotensive response is not a contraindication to further doses, which can be given usually without difficulty once the blood pressure has increased after volume expansion. In patients with congestive heart failure, with or without associated renal insufficiency,