LISINOPRIL AND HYDROCHLOROTHIAZIDE

The selection of a suitable antihypertensive dose of lisinopril and hydrochlorothiazide will depend upon the clinical evaluation of the patient. Lisinopril/hydrochlorothiazide should be taken once daily. The administration of the fixed combination lisinopril and hydrochlorothiazide is usually recommended after dosage titration with the individual components.

When clinically appropriate, a direct change from monotherapy to fixed combination may be considered. 5 mg tablets may be administrated in patients whose blood pressure is not adequately controlled by 10 or 20 mg lisinopril alone. A maximum daily dose of 40 mg lisinopril/ 25 mg hydrochlorothiazide should not be exceeded.

Diuretic Pretreatment The diuretic therapy should be stopped two to three days prior to the start of a treatment with lisinopril/hydrochlorothiazide. 5 mg dose. Renal impairment The combination lisinopril/hydrochlorothiazide is contraindicated in patients with severe renal impairment (creatinine clearance <30 ml/min).

In patients with creatinine clearance between 30 and 80 ml/min it may be used only after titration of the individual components. 4). Elderly patients Clinical studies on the combination of lisinopril and hydrochlorothiazide have not shown that age is associated with any changes in efficacy or tolerability.

See the above section on “Renal impairment”. Children and adolescents (<18years) Safety and efficacy of lisinopril/hydrochlorothiazide have not been established in children.

5mg tablets with the following frequencies: very common (>1/10), common (>1/100:<1/10), uncommon (>1/1000,<1/100), rare (>1/10000;<1/1000), very rare (<1/10000) including isolated reports. 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. Metabolism and nutrition disorders Uncommon: gout Nervous system and psychiatric disorders Common: dizziness, which generally responded to dosage reduction and seldom required discontinuation of therapy; headache, fatigue.

Uncommon: paraesthesia, asthenia Respiratory, thoracic and mediastinal disorder Common: dry and persistent cough, which disappears after discontinuation of therapy. Cardiac and vascular disorders Common: hypotension including orthostatic hypotension.

Uncommon: palpitation, chest pain, muscle spasms and muscle weakness Gastrointestinal disorders: Uncommon: diarrhoea, nausea, vomiting, indigestion, pancreatitis, dry mouth. Skin and subcutaneous tissue disorders Uncommon: rash. 4). Reproductive system and genitals and breast disorders Uncommon: impotence.

Others Rare: a complex of symptoms, consisting of one or more of the following: fever, vasculitis, myalgia, artralgia or arthritis, positive ANA test; increased ESR, eosinophilia, leukocytosis, rash, photosensibility or other dermatologic manifestations.

Findings in laboratory tests Changes in laboratory values have rarely been of clinical significance. Hyperglycaemia, hyperuricaemia and hyperkalaemia or hypokalaemia are seen occasionally. Mild and temporary increases in blood nitrogen urea and serum creatinine are usually seen in patients without pre-existing kidney failure.

If such increases are persistent, they generally disappear when treatment is discontinued. Bone marrow depression, manifested as anaemia and/or thrombocytopenia and/or leucopenia, has been reported. Agranulocytosis is reported rarely, although a causal connection has not been established.

5mg tablets, but it was rarely of clinical significance unless another cause of anaemia existed simultaneously. 5mg tablets has not been established. Haemolytic anaemia has been rarely reported.

Undesirable effects reported of the individual components:

Hydrochlorothiazide: Infections and infestations: silaldenitis Blood and lymphatic system disorders: leucopenia, neutropenia/agranulocytosis, thrombocytopenia, aplastic anaemia, haemolytic anaemia, bone marrow suppression. Metabolism and nutrition disorders: anorexia, hyperglycaemia, glucosuria, hyperuricaemia, electrolyte imbalance (including hyponatraemia, hypokalaemia, hypochloremic alkalosis and hypomagnesaemia),, increases in cholesterol and triglycerides.

Psychiatric disorders: restlessness, depression, sleep disturbance Nervous system disorders: loss of appetite, paraesthesia, light-headedness Eye disorders: xanthopsia, transient blurred vision Ear and labyrinth disorders: vertigo Cardiac disorders: postural hypotension, cardiac arrhythmias Vascular disorders: necrotising angiitis (vasculitis, cutaneous vasculitis) Respiratory, thoracic and mediastinal disorders: respiratory distress (including pneumonitis and pulmonatory oedema) Gastrointestinal disorders: gastric irritation, diarrhoea, constipation, pancreatitis Hepato-biliary disorders: jaundice (intrahepatic cholstatic jaundice) Skin and subcutaneous disorders: photosensitivity reactions, rash, cutaneous lupus erythematosus-like reactions, reactivation of cutaneous lupus erythematosus, urticaria, anaphylactic reactions, toxic epidermal necrolysis Musculoskeletal, connective tissue and bone disorders: muscle spasm Renal and urinary disorders: renal dysfunction, interstital nephritis General disorders: fever, weakness Lisinopril and other ACE inhibitors: Blood and the lymphatic system disorders: Rare: decreases in haemoglobin, decreases in haematocrit.

Very rare: bone marrow depression, anaemia, thrombocytopenia, leucopenia, neutropenia, agranulocytosis (see [Special warnings and precautions for use]), haemolytic anaemia, lymphadenopathy, autoimmune disease Metabolism and nutrition disorders Very rare: hypoglycaemia Nervous system and psychiatric disorders: Common: dizziness, headache Uncommon: mood alterations, paraesthesia, vertigo, taste disturbance, sleep disturbances.

4), palpitations, tachycardia. 4) Very rarely, it has been reported that in some patients the […]

Lisinopril Symptomatic hypotension Symptomatic hypotension is seen rarely in uncomplicated hypertensive patients. g. 8). In 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 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 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 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 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 may be necessary. Aortic and mitral valve stenosis / hypertrophic cardiomyopathy As with other ACE inhibitors, lisinopril 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.

2 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 with a 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, they should be discontinued and renal function should be monitored during the first weeks of lisinopril therapy. Some hypertensive patients with no apparent pre-existing renal vascular disease have developed increases in blood urea and serum creatinine, usually minor and transient, especially 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. Patients with renal transplantation As there is no experience with lisinopril in patients with recent renal transplantation administration of lisinopril is not recommended in these patients.

Hypersensitivity/angioedema Angioedema of the face, extremities, lips, tongue, glottis and/or larynx has been reported rarely in patients treated with angiotensin converting enzyme inhibitors, including lisinopril. This may occur at any time during therapy.

In such cases, lisinopril 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 complete and sustained resolution of symptoms has occurred.

3). g. AN 69)and during low-density lipoproteins (LDL) apheresis with dextran sulphate) 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 lipoprotein (LDL) apheresis In rare occasions, patients receiving ACE inhibitors during low-density lipoprotein (LDL) apheresis with dextran sulphate have experienced life-threatening anaphylactoid reactions.

These symptoms could be avoided by temporary discontinuation of the treatment with ACE inhibitors before each apheresis. g. hymenoptera venom) have sustained anaphylactoid reactions. In the same patients, these […]

1 or any other ACE-inhibitors • History of hypersensitivity to hydrochlorothiazide or other sulphonamide medicinal products • History of angioneurotic oedema relating to previous ACE-inhibitor therapy • Hereditaryor idiopathic angioneurotic oedema.

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