INNOZIDE

Posology The dosage of Innozide should be determined primarily by the experience with the enalapril maleate component. Adults Essential hypertension The usual dosage is one tablet, taken once daily. If necessary, the dosage may be increased to two tablets, taken once daily.

Prior diuretic therapy: symptomatic hypotension may occur following the initial dose of Innozide; this is more likely in patients who are volume and/or salt depleted as a result of prior diuretic therapy. The diuretic therapy should be discontinued for 2-3 days prior to initiation of therapy with Innozide.

e. moderate or severe renal insufficiency). In patients with creatinine clearance of >30 mL/min and <80 mL/min, Innozide should be used only after titration of the individual components. Use in the elderly In clinical studies the efficacy and tolerability of enalapril maleate and hydrochlorothiazide, administered concomitantly, were similar in both elderly and younger hypertensive patients.

Paediatric population Safety and effectiveness in children have not been established. Method of administration Oral use.

Innozide is usually well-tolerated. In clinical studies, side effects have usually been mild and transient, and in most instances have not required interruption of therapy. The most common side effects reported during clinical study with Innozide were headache and cough.

The following undesirable side effects have been reported for Innozide, enalapril alone or hydrochlorothiazide alone either during clinical studies or after the drug was marketed. Table 1. 4) Gastrointestinal Nausea Diarrhoea, abdominal Ileus, pancreatitis, Stomatitis/ap hthous Intestinal angioedem disorders pain vomiting, dyspepsia, constipation, anorexia, gastric irritations, dry mouth, peptic ulcer, flatulence** ulcerations, glossitis a Hepatobiliary disorders Hepatic failure, hepatic necrosis (may be fatal), hepatitis – either hepatocellula r or cholestatic, jaundice, cholecystitis (in particular in patients with pre- existing cholelithiasis ) Skin and subcutaneous tissue disorders Rash (exanthema) hypersensiti vity/angione urotic oedema: angioneuroti c oedema of the face, extremities, lips, tongue, glottis and/or larynx has been reported (see section Diaphoresis, pruritus, urticaria, alopecia Erythema multiforme, Stevens- Johnson syndrome, exfoliative dermatitis, toxic epidermal necrolysis, purpura, cutaneous lupus erythematosu s, erythroderma , pemphigus A symptom complex has been reported which may include some or all of the following: fever, serositis, vasculitis, myalgia/myositis, arthralgia/arthritis, a positive ANA, elevated ESR, eosinophilia, and leucocytosis.

4) manifestations may occur. Musculoskeletal, connective tissue, and bone disorders Muscle cramps† Arthralgia** Renal and urinary disorders Renal dysfunction, renal failure, proteinuria Oliguria, interstitial nephritis Reproductive system and breast disorders Impotence Gynecomasti a General disorders and administration site conditions Asthenia Chest pain, fatigue Malaise, fever Investigations Hyperkalae mia, increases in serum creatinine Increases in blood urea, hyponatraemi a Elevations of liver enzymes, elevations of serum bilirubin * Incidence rates were comparable to those in the placebo and active control groups in the clinical trials.

Enalapril Maleate - Hydrochlorothiazide Hypotension and Electrolyte Fluid Imbalance Symptomatic hypotension is rarely seen in uncomplicated hypertensive patients. 8). Regular determination of serum electrolytes should be performed at appropriate intervals in such patients.

Special attention should be paid to patients with ischemic heart or cerebrovascular disease in whom an excessive fall in blood pressure could result in a myocardial infarction or cerebrovascular accident. In hypertensive patients with heart failure, with or without associated renal insufficiency, symptomatic hypotension has been observed.

This is most likely to occur in those patients with more severe degrees of heart failure, as reflected by the use of high doses of loop diuretics, hyponatraemia or functional renal impairment. In these patients, therapy should be started under medical supervision and the patients should be followed closely whenever the dose of Innozide and/or diuretic is adjusted.

Similar considerations may apply to patients with ischaemic heart or cerebrovascular disease in whom an excessive fall in blood pressure could result in a 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 normal saline.

A transient hypotensive response is not a contra-indication to further doses, which can be given usually without difficulty once the blood pressure has increased after volume expansion. In some patients with heart failure who have normal or low blood pressure, additional lowering of systemic blood pressure may occur with Innozide.

This effect is anticipated, and usually is not a reason to discontinue treatment. If hypotension becomes symptomatic, a reduction of dose and/or discontinuation of the diuretic and/or Innozide may be necessary. Renal Function Impairment Renal failure has been reported in association with enalapril and has been mainly in patients with severe heart failure or underlying renal disease, including renal artery stenosis.

1. • Severe renal impairment (creatinine clearance ≤30 mL/min). • Anuria. • History of angioneurotic oedema associated with previous ACE-inhibitor therapy. • Hereditary or idiopathic angioedema. • Hypersensitivity to sulfonamide-derived drugs.

6). • Severe hepatic impairment. 1) • Combination with sacubitril/valsartan due to the increased risk of angioedema. Do not administer Innozide within 36 hours of switching to or from sacubitril/valsartan, a product containing a neprilysin inhibitor.

5).