LISINOPRIL +HCT

Primary Hypertension The usual dosage is one tablet, administered once daily. 5 mg tablets should be taken at approximately the same time each day. In general, if the desired therapeutic effect cannot be achieved in a period of 2 to 4 weeks at this dose level, the dose can be increased to two tablets administered once daily.

e. moderate or severe renal insufficiency). 5 mg tablets is not to be used as initial therapy in any patient with renal insufficiency. In patients with creatinine clearance of >30 and <80 ml/min, Zestoretic may be used, but only after titration of the individual components.

The recommended dose of lisinopril, when used alone, in mild renal insufficiency, is 5 to 10 mg. Prior diuretic treatment Symptomatic hypotension may occur following the initial dose; 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 Zestoretic. If this is not possible, treatment should be started with lisinopril alone, in a 5 mg dose. Safety and effectiveness in the children have not beed established.

Elderly No adjustment of dosage is required in the elderly. In clinical studies the efficacy and tolerability of lisinopril and hydrochlorothiazide, administered concomitantly, were similar in both elderly and younger hypertensive patients.

Lisinopril, within a daily dosage range of 20 to 80 mg, was equally effective in the elderly (65 years or over) and non-elderly hypersensitive patients, monotherapy with lisinopril was as effective in reducing diastolic blood pressure as monotherapy with either hydrochlorothiazide or atenolol.

In clinical studies, age did not affect the tolerability of lisinopril. Method of administration Oral use. Paediatric population The safety and efficacy in children have not been established.

The following undesirable effects have been observed and reported during treatment with lisinopril and/or hydrochlorothiazide with the following frequencies: Very common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1,000 to <1/100), Rare (≥1/10,000 to <1/1,000), Very rare (<1/10,000), Not known (cannot be estimated from the available data).

The most commonly reported ADRs are cough, dizziness, hypotension, and headache which may occur in 1 to 10% of treated patients. In clinical studies, side effects have usually been mild and transient, and in most instances have not required interruption of therapy.

4), urticaria, alopecia, psoriasis Very rare Diaphoresis, pemphigus, toxic epidermal necrolysis, Stevens-Johnson Syndrome, erythema multiforme, cutaneous pseudolymphoma ** Renal and urinary disorders Common Renal dysfunction Rare Uraemia, acute renal failure Very rare Oliguria/anuria Reproductive system and breast disorders Uncommon Impotence Rare Gynaecomastia General disorders and administration site conditions Uncommon Asthenia, fatigue Investigations Uncommon Increases in blood urea, increases in serum creatinine, hyperkalaemia Rare Hyponatraemia * Very rarely, it has been reported that in some patients the undesirable development of hepatitis has progressed to hepatic failure.

Patients receiving lisinopril-hydrochlorothiazide combination who develop jaundice or marked elevations of hepatic enzymes should discontinue lisinopril- hydrochlorothiazide combination and receive appropriate medical follow up. **A symptom complex has been reported which may include one or more of the following: fever, vasculitis, myalgia, arthralgia/arthritis, a positive antinuclear antibodies (ANA), elevated red blood cell sedimentation rate (ESR), eosinophilia and leucocytosis, rash, photosensitivity or other dermatological manifestations may occur.

1). Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is […]

Non-melanoma skin cancer An increased risk of non-melanoma skin cancer (NMSC) [basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)] with increasing cumulative dose of hydrochlorothiazide (HCT) exposure has been observed in two epidemiological studies based on the Danish National Cancer Registry.

Photosensitizing actions of HCT could act as a possible mechanism for NMSC. Patients taking HCT should be informed of the risk of NMSC and advised to regularly check their skin for any new lesions and promptly report any suspicious skin lesions.

Possible preventive measures such as limited exposure to sunlight and UV rays and, in case of exposure, adequate protection should be advised to the patients in order to minimize the risk of skin cancer. Suspicious skin lesions should be promptly examined potentially including histological examinations of biopsies.

8). g. 8). Regular monitoring of serum electrolytes should be performed at appropriate intervals in such patients. In patients at increased risk of symptomatic hypotension, initiation of therapy and dose adjustment should be monitored under close medical supervision.

Particular consideration applies to patients with ischaemic heart or cerebrovascular disease because an excessive fall in blood pressure could result in a myocardial infarction or a 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 contraindication for further doses. Following restoration of effective blood volume and pressure, reinstitution of therapy at reduced dosage may be possible; or either of the components may be used alone, as appropriate.

In some patients with heart failure who have normal or low blood pressure, additional lowering of systemic blood pressure may occur with lisinopril. This effect is anticipated and is not usually a reason to discontinue treatment. If hypotension becomes symptomatic, a reduction of dose or discontinuation of lisinopril-hydrochlorothiazide may be necessary.

5 mg tablets should be given with caution to patients with, mitral valve stenosis and obstruction in the outflow of the left ventricle such as aortic stenosis or hypertrophic cardiomyopathy. Dual blockade of the renin-angiotensin-aldosterone system (RAAS) There is evidence that the concomitant use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of hypotension, hyperkalaemia and decreased renal function (including acute renal failure).

1). If dual blockade therapy is considered absolutely necessary, this should only occur under specialist supervision and subject to frequent close monitoring of renal function, electrolytes and blood pressure. ACE-inhibitors and angiotensin II receptor blockers should not be used concomitantly in patients with diabetic nephropathy.

e. corresponds to moderate or severe renal insufficiency). 5 mg tablets should not be administered to patients with renal insufficiency (creatinine clearance less than or equal to 80 ml/min) until titration of the individual components has shown the need for the doses present in the combination tablet.

In patients with heart failure, hypotension following the initiation of therapy with ACE inhibitors may lead to some further impairment in renal function. Acute renal failure, usually reversible, has been reported in this situation.

In some patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney, who have been treated with ACE inhibitors, increases in blood urea and serum creatinine usually reversible upon discontinuation of therapy, have been seen.

This is especially likely in patients with renal insufficiency. If renovascular hypertension is also present, there is an increased risk of severe hypotension and renal insufficiency. In these patients, treatment should be started under close medical supervision with low doses and careful dose titration.

Since treatment with diuretics may be a contributory factor to the above, renal function should be monitored during the first few weeks of lisinopril-hydrochlorothiazide therapy. Some hypertensive patients with no apparent pre-existing renal disease have developed usually minor and transient increases in blood urea and serum creatinine when lisinopril has been given concomitantly with a diuretic.

This is more likely to occur in patients with pre-existing renal impairment. Dosage reduction and/or discontinuation of the diuretic and/or lisinopril may be required. Prior diuretic therapy The diuretic therapy should be discontinued for 2-3 days prior to initiation with lisinopril-hydrochlorothiazide.

If this is not possible, treatment should be started with lisinopril alone, in a 5 mg dose. Renal transplantation Lisinopril + HCT should not be used, since there is no experience with patients recently transplanted with a kidney. Anaphylactoid reactions in haemodialytic patients The use of Lisinopril + HCT is not indicated in patients […]

1. - Hypersensitivity to any other angiotensin converting enzyme (ACE) inhibitor. - Hypersensitivity to any sulphonamide-derived medicinal product. - Lisinopril + HCT is contraindicated in patients with a history of angioedema relating to previous treatment with an ACE inhibitor.

- Concomitant use of Lisinopril + HCT with sacubitril/valsartan therapy. 5). - Hereditary or idiopathic angioedema. 6). Severe renal impairment (creatinine clearance < 30 ml/min). Severe hepatic impairment. 1).