LISINOPRIL/HYDROCHLOROTHIAZIDE

Posology The selection of a suitable antihypertensive dose of lisinopril and hydrochlorothiazide will depend upon the clinical evaluation of the patient. The administration of the fixed combination lisinopril and hydrochlorothiazide is usually recommended after dose titration with the individual components.

When clinically appropriate a direct change from monotherapy to fixed combination may be considered. 4). 4). A maximum daily dose of 40 mg lisinopril/25 mg hydrochlorothiazide should not be exceeded. As with all other medicinal products taken once daily, the tablets should be taken approximately at the same time every day.

). In patients with creatinine clearance between 30 and 80 ml/min it may be used only after titration of the individual components. 4). Diuretic treated patients Symptomatic hypotension may occur following the initial dose; this is more likely in patients who are volume and/or salt depleted because of diuretic therapy.

Diuretics should be discontinued for 2-3 days before starting lisinopril/hydrochlorothiazide combination. If this is not possible, treatment should be started with lisinopril alone, in a 5 mg dose. Renal function and serum potassium should be monitored.

The subsequent dose of lisinopril should be adjusted according to blood pressure response. 5). Paediatric population Safety and efficacy of the combination of lisinopril and hydrochlorothiazide in children have not been established. Therefore, use in children is not recommended.

Elderly Clinical studies on the combination of lisinopril and hydrochlorothiazide have not shown that age is associated with any changes in efficacy or tolerability. However, in the elderly patients the renal function is more likely to be impaired and dose-adjustment should be made when appropriate.

In the elderly patients the dose should be adjusted carefully (titration of the individual components) See the above section on "Renal impairment". Method of administration Oral use

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 adverse drug reactions are cough, dizziness, hypotension, and headache which may occur in 1 to 10% of treated patients.

In clinical studies, adverse reactions have usually been mild and transient, and in most instances have not required interruption of therapy.

Lisinopril Blood and lymphatic system disorders:

Rare Very rare Decreases in haemoglobin, decreases in haematocrit. 4). 4), urticaria, alopecia, psoriasis Diaphoresis, pemphigus, toxic epidermal necrolysis, Stevens-Johnson Syndrome, erythema multiforme, cutaneous pseudolymphoma. ** Renal and urinary disorders Common Rare Very rare Renal dysfunction Uraemia, acute renal failure Oliguria/anuria Reproductive system and breast disorders Uncommon Rare Impotence Gynaecomastia General disorders and administration site conditions Uncommon Asthenia, fatigue Investigations Uncommon Rare Increases in blood urea, increases in serum creatinine, hyperkalaemia 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.

g. 8). Regular determination 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 cerebrovascular accident. 9%) solution. A transient hypotensive response is not a contraindication for further doses.

Following restoration of effective blood volume and pressure, reinstitution of therapy at reduced dose may be possible; or either of the components may be used appropriately alone. 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. As with other ACE-inhibitors lisinopril should be given with caution to patients with aortic stenosis or hypertrophic cardiomyopathy.

Renal impairment Thiazides may not be appropriate diuretics for use in patients with renal impairment and are ineffective at creatinine clearance values of 30 ml/min or below (corresponds to moderate or severe renal insufficiency).

Lisinopril/hydrochlorothiazide 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 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 angiotensin converting enzyme inhibitors, increases in blood urea and serum creatinine, usually reversible upon discontinuation of therapy have been seen.

1 - History of angioedema with previous ACE inhibitor therapy. - Hereditary or idiopathic angioedema. 1). - Concomitant use with sacubitril/valsartan therapy. 5).