Instructions Liprazid 20 tablets blister No. 30
Composition
active ingredients: lisinopril and hydrochlorothiazide;
1 tablet of Liprazid 20 contains lisinopril (calculated as 100% anhydrous lisinopril) - 20 mg, which corresponds to lisinopril dihydrate - 21.78 mg and hydrochlorothiazide (calculated as 100% dry matter) - 12.5 mg;
Excipients: Liprazid 20 – mannitol (E 421), corn starch, magnesium stearate, red iron oxide (E 172), calcium hydrogen phosphate dihydrate.
Dosage form
Pills.
Main physicochemical properties: round tablets with a biconvex surface, pink in color. Marbling and red-brown inclusions are allowed on the surface of the tablets.
Pharmacotherapeutic group
Agents that affect the renin-angiotensin system. Combined ACE inhibitor preparations. Lisinopril and diuretics. ATC code C09B A03.
Pharmacological properties
Pharmacodynamics
A combined antihypertensive drug containing the angiotensin-converting enzyme (ACE) inhibitor lisinopril and the diuretic hydrochlorothiazide.
Lisinopril inhibits ACE, which converts angiotensin I to angiotensin II. The reduction in angiotensin II leads to a direct decrease in aldosterone levels. This results in a decrease in total peripheral vascular resistance and systemic blood pressure.
Hydrochlorothiazide is a thiazide diuretic with antihypertensive activity. It reduces the reabsorption of electrolytes and water in the distal tubules of the kidneys, increases diuresis, as a result of which the total circulating blood volume decreases and elevated blood pressure decreases. A significant decrease in systolic and diastolic blood pressure occurs after 3-4 days of taking hydrochlorothiazide, and the optimal antihypertensive effect is observed after 3-4 weeks of using the drug.
The combination of lisinopril and hydrochlorothiazide produces a more pronounced hypotensive effect than either component alone.
Non-melanoma skin cancer: Results from two pharmacoepidemiological studies based on data from the Danish National Cancer Registry demonstrated a cumulative dose-dependent association between hydrochlorothiazide (HCTZ) and the occurrence of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC).
One study included a population of 71,533 patients with BCC and 8,629 patients with PCC, who were compared with 1,430,833 and 172,462 control patients, respectively. High doses of HT (≥ 50,000 mg cumulative) were associated with an adjusted hazard ratio (HR) of 1.29 (95% confidence interval (CI): 1.23-1.35) for BCC and 3.98 (95% CI: 3.68-4.31) for PCC. A clear cumulative dose-dependent relationship was observed for both BCC and PCC.
Another study showed a possible association between lip cancer (LC) and HRT use: 633 cases of lip cancer (LC) were matched to 63,067 controls using a random sampling strategy. A cumulative dose-dependent association was demonstrated with an adjusted HR of 2.1 (95% CI: 1.7-2.6), increasing to HR of 3.9 (3.0-4.9) for high doses (25,000 mg) and HR of 7.7 (5.7-10.5) for the highest cumulative dose (100,000 mg) (see section 4.4).
Pharmacokinetics
The bioavailability of lisinopril is about 30%. Food intake does not significantly affect the absorption of lisinopril. A small amount (6-10%) binds to plasma proteins. The initial effect after the use of lisinopril develops after 1 hour, the maximum concentration in the blood plasma is reached after 6-7 hours after administration. It is practically not biotransformed in the body, only about 7% of lisinopril is metabolized in the liver. Lisinopril partially penetrates the placental barrier. The main amount of the substance is excreted from the body unchanged in the urine. The half-life from the blood serum is 12 hours. The elimination of lisinopril in elderly patients is slowed down.
The diuretic effect of hydrochlorothiazide develops 2 hours after administration and reaches its maximum intensity after 3-4 hours, lasts 6-12 hours. The bioavailability of hydrochlorothiazide is 65-70%. About 40% binds to blood plasma proteins. Penetrates the placenta and is excreted in breast milk. Hydrochlorothiazide is not metabolized, it is excreted by the kidneys.
Indication
Arterial hypertension, if monotherapy with hydrochlorothiazide or lisinopril does not achieve the desired reduction in blood pressure.
Contraindication
Hypersensitivity to lisinopril, hydrochlorothiazide, other components of the drug or to other ACE inhibitors; hypersensitivity to sulfonamide derivatives; history of angioedema caused by previous use of ACE inhibitors; history of hereditary or idiopathic angioedema (Quincke's edema); mitral or aortic stenosis, hypertrophic cardiomyopathy with severe hemodynamic disorders; acute myocardial infarction with unstable hemodynamics; cardiogenic shock; severe renal failure (creatinine clearance < 30 ml/min), serum creatinine ≥ 220 μmol/l, anuria; bilateral renal artery stenosis or stenosis of the renal artery to a solitary kidney; condition after kidney transplantation; mechanical obstruction of the urinary tract; disorders of water-salt metabolism (treatment-resistant hyperkalemia/hypokalemia, refractory hyponatremia, hypovolemia); severe forms of diabetes mellitus; severe liver failure, hepatic encephalopathy; primary hyperaldosteronism; exacerbation of gout; porphyria; use with aliskiren-containing drugs in patients with diabetes mellitus or with impaired renal function (GFR < 60 ml/min/1.73 m2); use of high-flux membranes made of polyacrylonitrile sodium-2-methylallylsulfonate (e.g. AN 69) in hemodialysis; pregnant women or women planning to become pregnant (see section "Use during pregnancy and breastfeeding").
Interaction with other medicinal products and other types of interactions
Other antihypertensive drugs: possible enhancement of the hypotensive effect. Use with nitroglycerin and other organic nitrates or vasodilators may further reduce blood pressure. Ganglioblockers or adrenergic neurone blockers may be used in combination with lisinopril preparations only under strict supervision.
Combination with aliskiren-containing drugs should be avoided.
Dual blockade of the RAAS through the combined use of ACE inhibitors (including lisinopril), ARBs or aliskiren is associated with a higher frequency of side effects, such as hypotension, hyperkalemia, decreased renal function (including acute renal failure) compared with the use of a single RAAS-blocking drug (see sections "Contraindications", "Special instructions for use").
Lithium preparations: reversible increase in serum lithium levels and development of its toxic effects. Thiazide diuretics and ACE inhibitors reduce the renal clearance of lithium and significantly increase the risk of lithium intoxication. Therefore, the use of the combination of lisinopril/hydrochlorothiazide simultaneously with lithium is not recommended, but if such a combination is necessary, careful monitoring of serum lithium levels should be carried out.
Other diuretics: additive antihypertensive effects have been reported. In patients already receiving diuretics, especially those who have recently been given diuretics, the use of lisinopril may occasionally cause excessive reduction in blood pressure. Diuretic therapy should be discontinued 2-3 days before starting therapy with the combined drug lisinopril/hydrochlorothiazide to avoid the development of symptomatic hypotension. If this is not possible, treatment should be initiated with lisinopril alone.
Potassium-sparing diuretics, potassium supplements or potassium-containing salt substitutes: increased risk of hyperkalemia. Potassium loss due to thiazide diuretics is usually attenuated by the potassium-sparing effect of lisinopril. The use of potassium-sparing diuretics, potassium-sparing diuretics or potassium-containing salt substitutes may lead to significant increases in serum potassium, especially in patients with impaired renal function or diabetes mellitus. If concomitant use of lisinopril/hydrochlorothiazide and any of these agents proves necessary, they should be used with caution and with frequent monitoring of serum potassium.
Drugs that induce ventricular tachycardia of the torsade de pointes type: due to the risk of hypokalemia, the risk of developing cardiac arrhythmias, including ventricular tachycardia of the torsade de pointes type, increases with the concomitant use of hydrochlorothiazide and drugs whose effects are affected by changes in serum potassium levels:
Class I antiarrhythmics (e.g. quinidine, hydroquinidine, disopyramide); Class III antiarrhythmics (e.g. amiodarone, sotalol, dofetilide, ibutilide); Neuroleptics (e.g. thioridazine, chlorpromazine, levomepromazine, trifluoperazine, cyamemazine, sulpiride, sultopride, amisulpiride, tiapride, pimozide, haloperidol, droperidol); Others (e.g. bepridil, cisapride, diphemanil, intravenous erythromycin, halofantrine, mizolastine, pentamidine, terfenadine, intravenous vincamine).
Nonsteroidal anti-inflammatory drugs (NSAIDs), including selective COX-2 inhibitors, acetylsalicylic acid ≥ 3 g/day, non-selective NSAIDs: with prolonged use of NSAIDs, the hypotensive and diuretic effects of ACE inhibitors and thiazides are reduced. Concomitant use of NSAIDs and ACE inhibitors causes an additive effect on the increase in serum potassium, which can lead to deterioration of renal function. These effects are usually reversible. In isolated cases, acute renal failure may occur, especially in cases of impaired renal function, for example, in elderly patients or in patients with dehydration. NSAIDs may enhance the effect of hydrochlorothiazide on serum potassium, reduce the natriuretic effect of thiazides; the risk of NSAID-induced renal dysfunction increases.
Trimethoprim, heparin: Concomitant use of ACE inhibitors and thiazides with trimethoprim increases the risk of hyperkalemia and renal dysfunction.
Hypoglycemic agents (insulins, oral hypoglycemic agents): Epidemiological studies indicate that concomitant use of ACE inhibitors and antidiabetic agents may potentiate the blood glucose-lowering effects with a risk of hypoglycemia. The likelihood of such an effect is particularly high during the first weeks of combined treatment and in cases of impaired renal function. Dose adjustment of antidiabetic agents may be necessary.
Gold preparations: Nitritoid reactions (symptoms of vasodilation including flushing, nausea, dizziness, hypotension, which may be very significant) following injection of gold (e.g. sodium aurothiomalate) have been reported more frequently in patients treated with ACE inhibitors.
Sympathomimetics: the hypotensive effect of ACE inhibitors may be reduced.
Estrogens, corticosteroids: possible reduction in the antihypertensive effect of ACE inhibitors due to fluid retention in the body.
Amphotericin B (parenteral), carbenoxolone, corticosteroids, corticotropin (ACTH), or stimulant laxatives: Hydrochlorothiazide may exacerbate electrolyte imbalance, especially hypokalemia.
Calcium salts and vitamin D: Thiazide diuretics may reduce calcium excretion and increase plasma calcium levels. Serum calcium levels should be monitored and the dose of calcium/vitamin D should be adjusted.
Cardiac glycosides: increased likelihood of toxic effects of glycosides (including increased ventricular excitability) due to the development of thiazide-induced hypokalemia and hypomagnesemia.
Cholestyramine and colestipol: The absorption of hydrochlorothiazide may be delayed or reduced by up to 85% in the presence of anionic resins. Therefore, sulfonamide diuretics should be administered at least 1 hour before or 4-6 hours after taking these drugs.
Antacids: The bioavailability of lisinopril may be reduced, so the drug should be taken 1-2 hours before or 1-2 hours after taking an antacid.
Non-depolarizing muscle relaxants (e.g. tubocurarine chloride): hydrochlorothiazide potentiates the effects of these drugs and increases sensitivity to tubocurarine.
Sotalol: Thiazide-induced hypokalemia may increase the risk of sotalol-induced arrhythmias.
Allopurinol: Concomitant use of ACE inhibitors and allopurinol increases the risk of renal damage and may lead to an increased risk of leukopenia. Increased risk of hypersensitivity reactions.
Other drugs for the treatment of gout (probenecid, sulfinpyrazone): the dose of uricosuric drugs may need to be increased, as hydrochlorothiazide may increase serum uric acid levels.
Cyclosporine: Concomitant use of ACE inhibitors and cyclosporine increases the risk of kidney damage and hyperkalemia. Concomitant use of diuretics may increase the risk of hyperuricemia and gout-like complications.
Lovastatin: Concomitant use of ACE inhibitors and lovastatin increases the risk of hyperkalemia.
Aldesleukin: increased hypotensive effect of ACE inhibitors.
Agents that suppress bone marrow function: increased risk of neutropenia and/or agranulocytosis.
Cytostatics, immunosuppressive drugs, procainamide: use with ACE inhibitors may lead to an increased risk of leukopenia.
Cytotoxic drugs (e.g. cyclophosphamide, methotrexate): thiazides may reduce the renal excretion of cytotoxic drugs and enhance their myelosuppressive effects.
Pressor amines (e.g., norepinephrine, epinephrine): There may be a reduction in response to pressor amines, but not enough to preclude their use.
Barbiturates, diazepam, narcotic drugs: possible potentiation of the effect on the development of arterial and orthostatic hypotension.
Anticholinergics (e.g. atropine, biperiden): increased bioavailability of thiazide diuretics due to decreased gastrointestinal motility and gastric emptying rate.
Salicylates: In the case of high doses of salicylates, hydrochlorothiazide may enhance their toxic effect on the central nervous system.
Methyldopa: Isolated cases of hemolytic anemia have been reported when used with hydrochlorothiazide.
Beta-blockers, diazoxide: possible increase in their hyperglycemic effect due to thiazides.
Amantadine: Hydrochlorothiazide may increase the risk of adverse reactions to amantadine.
Carbamazepine: risk of hyponatremia. Electrolyte levels should be monitored.
Iodinated contrast media: In case of diuretic-induced dehydration, the risk of acute renal failure increases, especially with high doses of iodine preparations. Rehydration should be performed before the use of iodinated contrast media.
Tissue plasminogen activators, immunosuppressants such as mTOR inhibitors (e.g. temsirolimus, sirolimus, everolimus): possible increased risk of angioedema.
Alcohol: may enhance the hypotensive effect of any antihypertensive drugs.
Effect on laboratory test results: due to their effect on calcium metabolism, thiazides may affect the results of parathyroid function tests.
The drug can be used simultaneously with acetylsalicylic acid (in cardiological doses), thrombolytics, beta-blockers and/or nitrates under the supervision of a physician.
Lisinopril preparations should be used with caution in patients with acute myocardial infarction within 6-12 hours after streptokinase administration due to the risk of developing arterial hypotension.
Application features
Non-melanoma skin cancer.
An increased risk of non-melanoma skin cancer (NMSC) with increasing cumulative dose of GCS has been found in two pharmacoepidemiological studies. The photosensitizing effect of GCS may act as a possible mechanism for the development of this pathology.
Patients taking HCT alone or in combination with other drugs should be informed of the risk of developing NMSC, especially with long-term use, of the need for regular skin examinations and of the immediate reporting to the physician of new lesions or any suspicious skin growths, changes in skin lesions or moles.
To reduce the risk of skin cancer, patients should be informed about possible preventive measures, such as limiting exposure to sunlight and UV radiation, and in case of exposure, about the need for adequate skin protection. Suspicious skin lesions should be examined as soon as possible, including histological examination of biopsy material.
Patients who have previously had NMSR may also need to reconsider the use of HTZ.
Symptomatic hypotension
Symptomatic hypotension is rare in patients with uncomplicated hypertension and is more likely to occur in patients with volume depletion or electrolyte imbalance (including hyponatremia, hypochloraemic alkalosis, hypomagnesaemia or hypokalaemia), e.g. from diuretic therapy, a low-salt diet, dialysis, diarrhoea, vomiting or severe renin-dependent hypertension. These patients should have regular serum electrolyte measurements. In patients at increased risk of symptomatic hypotension, initiation of therapy and dose adjustment should be carried out under close medical supervision. Particular caution is required in patients with ischaemic heart disease or cerebrovascular disease, in whom an excessive decrease in blood pressure could lead to myocardial infarction or stroke.
In case of hypotension, the patient should be placed on his back and, if necessary, an intravenous infusion of saline solution should be given. Transient hypotension during treatment with the drug is not a contraindication for its further use. After normalization of blood pressure and restoration of effective blood volume, it is possible to resume therapy with lisinopril/hydrochlorothiazide in a reduced dosage or with one of the components separately.
In some patients with heart failure and normal or low blood pressure, lisinopril may further reduce systemic blood pressure. This effect is expected and is not usually a reason for discontinuation of treatment. If hypotension becomes symptomatic, it may be necessary to reduce the dose or discontinue the combination drug lisinopril/hydrochlorothiazide.
Dual blockade of the renin-angiotensin-aldosterone system (RAAS)
The concomitant use of ACE inhibitors (including lisinopril), angiotensin II receptor blockers (ARBs) or aliskiren increases the risk of hypotension, hyperkalemia and decreased renal function (including acute renal failure). Therefore, dual blockade of the RAAS by the combined use of ACE inhibitors with ARBs or aliskiren is not recommended.
If dual RAAS blockade is considered absolutely necessary, it should only be done under close specialist supervision and with frequent, careful monitoring of kidney function, blood electrolyte levels (especially potassium), and blood pressure.
ACE inhibitors and ARBs should not be used concomitantly in patients with diabetic nephropathy.
Symptomatic hypotension may occur after the initial dose of lisinopril/hydrochlorothiazide. This is more likely in patients who are dehydrated and/or volume-depleted from previous diuretic therapy. Diuretic therapy should be discontinued 2-3 days before starting lisinopril/hydrochlorothiazide. If this is not possible, treatment should be initiated with lisinopril 5 mg alone.
Aortic and/or mitral valve stenosis/hypertrophic cardiomyopathy.
As with other ACE inhibitors, lisinopril is not recommended for use in patients with mitral valve stenosis and left ventricular outflow obstruction (e.g., aortic stenosis or hypertrophic cardiomyopathy).
Kidney dysfunction
Thiazides may not be appropriate diuretics for use in patients with impaired renal function. They are ineffective in patients with creatinine clearance of 30 mL/min or less (moderate or severe renal impairment).
The combination drug lisinopril/hydrochlorothiazide should not be used as initial therapy in any patient with impaired renal function.
Lisinopril/hydrochlorothiazide should not be administered to patients with renal impairment (creatinine clearance ≤ 80 ml/min) unless titration of the individual active substances of the drug demonstrates the need for the doses contained in the combination tablet.
In patients with heart failure, hypotension occurring after initiation of ACE inhibitor therapy may lead to further deterioration of renal function with the possible subsequent development of reversible (after drug withdrawal) acute renal failure.
Some hypertensive patients without overt renal disease may experience slight transient increases in serum urea and creatinine, particularly when lisinopril is used concomitantly with diuretics. This is more likely to occur in patients with pre-existing renal impairment. This may require dose reduction and/or discontinuation of the diuretic and/or lisinopril.
Patients after kidney transplantation
There is no experience in the use of the drug in patients with a recent kidney transplant, therefore the drug should not be used in this group of patients.
Anaphylactoid reactions during hemodialysis
The use of lisinopril/hydrochlorothiazide is not indicated in patients requiring dialysis for renal failure.
Anaphylactoid reactions have been reported in patients undergoing hemodialysis with high-flux membranes (e.g. AN 69) and concomitant treatment with ACE inhibitors. In such patients, it is recommended that a different type of dialysis membrane or a different class of antihypertensive drug be used.
Anaphylactoid reactions during low-density lipoprotein (LDL) apheresis
Life-threatening anaphylactoid reactions have been reported rarely in patients receiving ACE inhibitors during LDL apheresis with dextran sulfate. To avoid these reactions, ACE inhibitors should be temporarily discontinued prior to each apheresis procedure.
Liver disease
Thiazides should be used with caution in patients with impaired liver function or progressive liver disease, since minor changes in fluid and electrolyte balance can precipitate sudden hepatic coma.
Very rarely, the use of ACE inhibitors has been associated with a syndrome that begins with cholestatic jaundice or hepatitis and progresses to fulminant hepatic necrosis, sometimes with fatal outcome. The mechanism of this syndrome is unknown. If patients taking lisinopril/hydrochlorothiazide develop jaundice or marked elevations of serum liver enzymes, the drug should be discontinued and the patient should be observed until symptoms resolve.
Surgery/general anesthesia
During major surgery or during anesthesia with drugs that cause hypotension, lisinopril may block the formation of angiotensin II due to compensatory renin release, causing a pronounced and unpredictable decrease in blood pressure. In the event of hypotension that can be explained by this mechanism, it should be corrected by increasing the BCC.
Metabolic and endocrine effects
Thiazide diuretic therapy may be associated with increases in plasma cholesterol, free bilirubin (due to displacement from albumin binding) and triglycerides.
Thiazides may reduce the level of protein-bound iodine in the blood plasma without signs of thyroid dysfunction.
In some patients, the use of thiazide diuretics may provoke hyperuricemia and/or aggravate/trigger gout attacks in predisposed patients. However, lisinopril may increase uric acid excretion and thus may attenuate the hyperuricemic effect of hydrochlorothiazide.
Electrolyte imbalance
All patients receiving diuretic therapy should have periodic serum electrolyte determinations to detect possible fluid and electrolyte imbalance.
Thiazides, including hydrochlorothiazide, may cause fluid and electrolyte imbalances, including hypovolemia, hyponatremia, hypokalemia, hypomagnesemia, and hypochloremic alkalosis. Determination of serum and urine electrolyte levels is particularly important when the patient is experiencing excessive vomiting and/or diarrhea or is receiving parenteral fluids. Warning signs of fluid and electrolyte imbalance, regardless of cause, include dry mouth, thirst, weakness, lethargy, drowsiness, restlessness, confusion, convulsions, muscle pain or cramps, muscular fatigue, hypotension, oliguria, tachycardia, nausea, and vomiting.
The drug should be prescribed with caution to patients on a salt-free diet.
Dilutional hyponatremia may occur in patients with edema in hot weather. Chloride deficiency is usually minor and does not require treatment. Thiazides increase urinary magnesium excretion, which may lead to hypomagnesemia.
Thiazides may also reduce urinary calcium excretion and, as a result, cause a slight transient increase in its level in the blood plasma. Significant hypercalcemia may be a manifestation of latent hyperparathyroidism. Thiazides should be discontinued before testing parathyroid function.
Hyperkalemia
Increases in serum potassium have been observed in some patients treated with ACE inhibitors, including lisinopril. Risk factors for the development of hyperkalemia include renal insufficiency, diabetes mellitus, concomitant use of potassium-sparing diuretics, potassium supplements or salt substitutes containing potassium, or other drugs that increase serum potassium (e.g. heparin, trimethoprim). If the use of these drugs during treatment with ACE inhibitors is considered necessary, regular monitoring of serum potassium is recommended.
Monitoring of blood electrolytes is particularly important in patients receiving potassium-sparing diuretics and ACE inhibitors or ARBs for heart failure. The lowest effective doses of potassium-sparing diuretics and ACE inhibitors/ARBs should also be used in such cases. In the event of hyperkalemia, consideration should be given to interrupting or discontinuing treatment.
Diabetes mellitus
Patients taking oral antidiabetic agents or insulin should have close glycemic control, especially during the first month of treatment with ACE inhibitors.
Hypersensitivity/angioedema
Angioedema of the face, extremities, lips, tongue, epiglottis, vocal cords and/or larynx has been reported in isolated cases in patients treated with ACE inhibitors, including lisinopril. Angioedema may occur at any time during treatment. In such cases, lisinopril should be discontinued immediately, appropriate treatment should be given and the patient should be observed until symptoms resolve.
Even in cases where swelling is limited to the tongue and there are no signs of respiratory distress, patients may require prolonged observation, as treatment with antihistamines and corticosteroids may not be sufficient.
Very rarely, fatalities have been reported as a result of angioedema of the larynx or tongue. If the swelling extends to the tongue, vocal cords or larynx, airway obstruction may occur, especially in patients who have previously undergone respiratory surgery. In such cases, emergency treatment (adrenaline (epinephrine) administration and/or maintenance of a patent airway) should be initiated immediately. The patient should be kept under close medical supervision until complete and sustained resolution of symptoms.
Angioedema with the use of ACE inhibitors occurred more often in representatives of the Negroid race than in patients of other races.
Patients with a history of angioedema unrelated to ACE inhibitor therapy may be at increased risk of developing angioedema when treated with ACE inhibitors.
Patients receiving thiazides may experience hypersensitivity reactions (with or without a history of allergy or bronchial asthma). The use of the drug may exacerbate connective tissue diseases, including systemic lupus erythematosus.
Patients receiving ACE inhibitors during desensitization therapy with allergens (e.g., hymenoptera venom) have developed prolonged anaphylactoid reactions. These reactions can be avoided by withholding ACE inhibitors during desensitization, but accidental re-administration of ACE inhibitors has been shown to precipitate anaphylactoid reactions.
Neutropenia/agranulocytosis/thrombocytopenia/anemia.
Neutropenia/agranulocytosis, thrombocytopenia and anemia have been reported in patients receiving ACE inhibitors. Neutropenia is rare in patients with normal renal function and in the absence of other complicating factors. Neutropenia and agranulocytosis are reversible upon discontinuation of ACE inhibitors.
Lisinopril should be used with particular caution in patients with diffuse connective tissue diseases, in treatment with immunosuppressants, allopurinol or procainamide, as well as in the combination of these complicating factors, especially in the presence of pre-existing renal impairment.
Some of these patients have developed severe infections, sometimes unresponsive to intensive antibiotic therapy. Periodic monitoring of white blood cell counts is recommended in such patients when using lisinopril and patients should be advised to report any signs of infection to their physician.
Choroidal effusion, acute myopia, and secondary angle-closure glaucoma
Hydrochlorothiazide, which is part of the drug, can cause an idiosyncratic reaction, leading to the appearance of choroidal effusion with visual field defect, the development of acute transient myopia and acute angle-closure glaucoma. Symptoms are characterized by an acute onset of decreased visual acuity and/or eye pain and usually develop from a few hours to a few weeks after the start of treatment with hydrochlorothiazide.
Untreated acute angle-closure glaucoma may lead to permanent vision loss. The first step is to discontinue hydrochlorothiazide as soon as possible. Urgent medical or surgical treatment should be considered if intraocular pressure remains uncontrolled. A history of allergy to sulfonamides or penicillins may be a risk factor for the development of acute angle-closure glaucoma.
Ethnic characteristics.
Angioedema has been reported more frequently in black patients treated with ACE inhibitors than in non-black patients. As with other ACE inhibitors, the antihypertensive effect of lisinopril is less pronounced in black patients than in non-black patients, possibly because of a higher prevalence of low-renin states in black hypertensive patients.
Cough
Nonproductive persistent cough has been reported with ACE inhibitors, which resolves after discontinuation of the drug. Cough caused by ACE inhibitors should be differentiated from cough in other diseases.
Primary hyperaldosteronism
In patients suffering from primary hyperaldosteronism, ACE inhibitors are ineffective, so the drug should not be used in this group of patients.
Lithium
The concomitant use of lithium and lisinopril is generally not recommended.
Elderly patients
According to clinical studies, the efficacy and tolerability of concomitant use of lisinopril and hydrochlorothiazide were similar in both elderly and younger patients with arterial hypertension.
No dosage adjustment is necessary in elderly patients. If an elderly patient has decreased renal function, the initial dose of lisinopril should be adjusted (see Renal impairment).
Pregnancy
ACE inhibitors should not be initiated during pregnancy. Unless continued ACE inhibitor therapy is considered essential, patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, ACE inhibitor treatment should be stopped immediately, and, if appropriate, alternative therapy should be started (see sections 4.3 and 4.8).
Photosensitivity reactions
Photosensitivity reactions have been reported during treatment with thiazides. If photosensitivity reactions occur during treatment, it is recommended to discontinue the drug. If the doctor considers that the drug should be re-administered, it is recommended to protect areas of the body exposed to sunlight or artificial UV radiation and to limit exposure to the sun.
Anti-doping test
The hydrochlorothiazide contained in this medicine may cause a false-positive result in a doping test.
The antihypertensive effect of hydrochlorothiazide may be enhanced after sympathectomy.
Drinking alcohol is not recommended during treatment with Liprazid.
Ability to
