TEVA LISINOPRIL AND 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 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 20 mg lisinopril alone. A maximum daily dose of 40 mg lisinopril/ 25 mg hydrochlorothiazide should not be exceeded.

Diuretic pre-treatment The diuretic therapy should be stopped two to three days prior to the start of a treatment with lisinopril/hydrochlorothiazide. 5 mg dose. Special populations 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 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”. Paediatric population Safety and efficacy of lisinopril/hydrochlorothiazide have not been established in children. Method of administration Lisinopril/hydrochlorothiazide should be taken once daily.

Clinical studies have shown that the undesirable effects of the combination preparation are similar to the ones already reported with lisinopril and hydrochlorothiazide separately. 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 (>1/1000 to <1/100), rare (>1/10000 to1/1000), very rare (<1/10000), 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.

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 disorders common: dry and persistent cough, which disappeared 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.

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 dermatological manifestations.

Laboratory test values Fluctuations in laboratory values were rarely of clinical importance. Hyperglycaemia, hyperuricaemia, hyperkalemia or hypokalaemia have been reported incidentally. Increases in blood cholesterol and triglyceride concentrations may be observed in thiazide treatment.

A slight increase in blood urea level and serum creatinine are usually found in patients without a history of decreased renal function. When an increase is observed, this will usually disappear after stopping the treatment. Bone marrow depression, which manifests itself as anaemia and/or thrombocytopenia and/or leucopenia, has been reported.

Agranulocytosis is reported in rare cases, but a clear relation to the combination preparation could not be determined. Small decreases in haemoglobin and haematocrit values are frequently reported in patients with hypertension, but were rarely of clinical significance unless other anaemia causes existed.

Increases in liver enzymes and/or serum bilirubin have been noted rarely, but a causal link to lisinopril/hydrochlorothiazide has not been determined. Haemolytic anaemia has been reported rarely.

Undesirable effects reported of the individual components:

Hydrochlorothiazide (frequencies not known unless otherwise specified): Infections and infestations sialoadenitis Neoplasms benign, malignant and unspecified (incl cysts and polyps) non-melanoma skin cancer (Basal cell carcinoma and Squamous cell carcinoma) Blood and lymphatic system disorders leucopenia, neutropenia/agranulocytosis, thrombocytopenia, aplastic anaemia, haemolytic anaemia, bone marrow depression.

Metabolism and nutrition disorders anorexia, hyperglyceamia, glucosuria, hyperuricemia, electrolyte imbalance (including hyponatraemia hypokalaemia, hypochloremic alkalosis and hypomagnesaemia), increases in cholesterol and triglycerides, gout.

4) (frequency: very rare) Gastrointestinal disorders gastric irritation, diarrhoea, constipation, pancreatitis Hepato-biliary disorders jaundice (intrahepatic cholstatic jaundice) Skin and subcutaneous disorders photosensivity reactions, rash, cutaneous lupus erythematosus, systemic lupus erythematosus, cutaneous lupus erythematosus-like reactions, reactivation of cutaneous lupus erythematosus, urticaria, anaphylactic reactions, toxic epidermal necrolysis Musculoskeletal, connective tissue and bone disorders muscle spasm, muscle weakness Renal and urinary disorders renal dysfunction, interstitial nephritis General disorders fever, weakness Lisinopril and other ACE inhibitors: Blood and the lymphatic system disorders rare: decreases in haemoglobin, decreases in haematocrit.

4), haemolytic anaemia, lymphadenopathy, autoimmune disease Metabolism and nutrition disorders very rare: hypoglycaemia Nervous system and psychiatric disorders common: dizziness, headache, syncope uncommon: mood alterations, depressive symptoms, hallucinations, paraesthesia, vertigo, taste disturbance, sleep disturbances.

rare: mental confusion, olfactory disorder. 4), palpitations, tachycardia. 4) uncommon: rhinitis very […]

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. 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 considerations applies to patients with ischaemic heart or cerebrovascular disease because 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. 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 appropriately 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 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 Should not be used, since there is no experience with lisinopril in patients with recent renal transplantation.

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.

Angiotensin converting enzyme inhibitors cause a higher rate of angioedema in black patients than in non-black patients. 3). 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 lisinopril. 5). g. g. 5). Caution should be used when starting racecadotril, mTOR inhibitors […]

1. • Hypersensitivity to hydrochlorothiazide or other sulphonamide medicinal products • History of angioedema relating to previous ACE-inhibitor therapy • Hereditary or idiopathic angioedema. 1) • Concomitant use with sacubitril/valsartan therapy.

5).