Instructions for use Co-Irbesan film-coated tablets 300 mg + 12.5 mg No. 28
Composition
active ingredient: irbesartan; hydrochlorothiazide;
1 film-coated tablet contains irbesartan 150 mg and hydrochlorothiazide 12.5 mg or irbesartan 300 mg and hydrochlorothiazide 12.5 mg;
excipients: lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, colloidal anhydrous silica, magnesium stearate, coating *Opadry Pink OY – 34948.
*Opadry Pink OY – 34948 coating composition: hydroxypropylmethylcellulose (2910), polyethylene glycol 400, titanium dioxide (E 171), iron oxide red (E 172).
Dosage form
Film-coated tablets.
Main physicochemical properties:
150 mg/12.5 mg tablets: oval, biconvex, pink, film-coated tablets with a breakline on one side;
300 mg/12.5 mg tablets: oblong, pink, film-coated tablets with a breakline on one side.
Pharmacotherapeutic group
Combined preparations of angiotensin II inhibitors. ATX code C09D A04.
Pharmacological properties
Pharmacodynamics.
Co-Irbesartan® is a combination of the angiotensin-II receptor antagonist irbesartan and the thiazide diuretic hydrochlorothiazide. The combination of these components has an additive antihypertensive effect, in which blood pressure is reduced significantly more than when either component is used alone.
Irbesartan is a potent, orally active, selective angiotensin II receptor (AT1 subtype) antagonist. It can block all actions of angiotensin II mediated by the AT1 receptor, regardless of the source or route of synthesis of angiotensin II. Selective antagonism of angiotensin II (AT1) receptors results in increases in renin and plasma angiotensin II levels and decreases in plasma aldosterone concentrations. In particular, irbesartan, when used at recommended doses in patients without risk of electrolyte imbalance, does not significantly affect serum potassium levels. Irbesartan does not inhibit ACE (kininase II), the enzyme that generates angiotensin II, and also degrades bradykinin to inactive metabolites. Irbesartan does not require metabolic activation.
Hydrochlorothiazide is a thiazide diuretic. The mechanism of the antihypertensive effect of thiazide diuretics is not yet fully understood. Thiazides affect the mechanisms of electrolyte reabsorption in the renal tubules, directly increasing the excretion of sodium and chloride in approximately equal amounts. Due to the diuretic action of hydrochlorothiazide, the volume of blood plasma decreases, plasma renin activity increases, aldosterone secretion increases, as a result of which the loss of potassium and bicarbonate in the urine increases and the concentration of potassium in the blood serum decreases. Presumably, due to the blockade of the renin-angiotensin-aldosterone system, there is a tendency to compensate for the loss of potassium when irbesartan is used simultaneously. When using hydrochlorothiazide, diuresis begins after 2 hours, and the peak effect occurs at approximately 4 hours, while its effect lasts for approximately 6-12 hours.
The combination of hydrochlorothiazide and irbesartan resulted in a dose-dependent additional reduction in blood pressure within the therapeutic dose range. The addition of 12.5 mg of hydrochlorothiazide to 300 mg of irbesartan once daily in patients inadequately controlled on 300 mg of irbesartan alone resulted in a placebo-corrected reduction in diastolic blood pressure to a trough value (24 hours after dosing) of 6.1 mm Hg. The combination of 300 mg of irbesartan and 12.5 mg of hydrochlorothiazide resulted in an overall reduction in systolic/diastolic blood pressure of 13.6/11.5 mm Hg. excluding placebo.
When using 150 mg of irbesartan and 12.5 mg of hydrochlorothiazide once a day, a decrease in mean systolic/diastolic blood pressure with placebo-corrected data of 12.9/6.9 mm Hg was observed (24 hours after administration) in patients with mild to moderate hypertension. The peak effect was observed after 3-6 hours. When assessing blood pressure by ambulatory monitoring, the simultaneous use of 150 mg of irbesartan and 12.5 mg of hydrochlorothiazide once a day showed a consistent decrease in blood pressure over 24 hours with a mean decrease in systolic/diastolic blood pressure over 24 hours of 15.8/10 mm Hg, excluding data obtained from the use of placebo. When measured by ambulatory blood pressure monitoring, the trough-to-peak effect of the 150 mg/12.5 mg dose was 100%. The trough-to-peak effects, measured by blood pressure measurements during doctor visits, were 68% and 76%, respectively. These effects are observed over 24 hours without excessive reduction in blood pressure relative to the peak value and represent a safe and effective reduction in blood pressure over the duration of a single daily dose.
In patients not adequately controlled on 25 mg of hydrochlorothiazide alone, the addition of irbesartan provided an additional mean reduction in systolic/diastolic blood pressure, excluding placebo, of 11.1/7.2 mmHg.
The blood pressure lowering effect of irbesartan in combination with hydrochlorothiazide is evident after the first dose and lasts for 1-2 weeks, with the maximum effect occurring after 6-8 weeks. In long-term follow-up studies, the effect of irbesartan/hydrochlorothiazide was maintained for a period of more than one year. Although not specifically stated for Co-Irbesan®, no rebound hypertension was observed with either irbesartan or hydrochlorothiazide.
The effect of irbesartan and hydrochlorothiazide on morbidity and mortality has not been studied. Studies have shown that long-term treatment with hydrochlorothiazide reduces the risk of cardiovascular mortality.
There is no difference in the response to the use of Co-Irbesartan® depending on age or gender. As with other drugs that affect the renin-angiotensin system, in patients of the Negroid race with hypertension, the response to monotherapy with irbesartan is significantly lower. When irbesartan is used simultaneously with a low dose of hydrochlorothiazide (for example, 12.5 mg per day), the antihypertensive response in such patients approaches that of patients of other races.
The efficacy and safety of Co-Irbesartan® as initial therapy for severe arterial hypertension (defined as systolic blood pressure ≥ 110 mm Hg) was evaluated in a multicenter, randomized, double-blind, active-controlled, 8-week multi-arm study.
47% of patients receiving the combination achieved a minimum systolic blood pressure < 90 mm Hg compared with 33.2% of patients receiving irbesartan (p=0.0005). The mean baseline blood pressure was approximately 172/113 mm Hg in each group of participants and the reduction in systolic/diastolic blood pressure at week 5 was 30.8/24.0 mm Hg and 21.1/19.3 mm Hg for irbesartan/hydrochlorothiazide and irbesartan, respectively (p<0.0001).
In the studies, the types and number of adverse events reported in patients treated with the combination were similar to the adverse event profile in patients treated with monotherapy. No cases of loss of consciousness were reported during the studies. Decreased blood pressure was reported in 0.6% and 0% of patients, and dizziness in 2.8% and 3.1% of patients, respectively, in the combination and monotherapy groups.
Pharmacokinetics.
Concomitant use of hydrochlorothiazide and irbesartan does not affect the pharmacokinetics of either component of the drug.
Irbesartan and hydrochlorothiazide are orally active drugs and do not require biological transformation to be active. After oral administration of Co-Irbesan®, the absolute oral bioavailability is 60-80% and 50-80%, respectively, for irbesartan and hydrochlorothiazide. The bioavailability of Co-Irbesan® is not affected by food intake. Peak plasma concentrations are reached 1.5-2 hours after oral administration for irbesartan and 1-2.5 hours for hydrochlorothiazide.
Irbesartan exhibits linear and dose-proportional pharmacokinetics over the dose range of 10 to 600 mg. Increased absorption has been observed at doses below 600 mg; the mechanism is not clear. Total renal clearance is 157-176 and 3-3.5 ml/min, respectively. The terminal half-life of irbesartan is 11-15 hours. Steady-state plasma concentrations are reached within 3 days of starting a once-daily regimen. Limited accumulation of irbesartan (<20%) is observed in plasma after repeated daily dosing. In a study, slightly higher plasma concentrations of irbesartan were observed in female hypertensive patients. However, no difference in half-life and accumulation of irbesartan was observed. No dosage adjustment is necessary for female patients. The values of the area under the concentration-time curve and the maximum concentration for irbesartan were also slightly higher in elderly patients (≥ 65 years) than in young patients (18-40 years). However, the terminal half-life was not significantly different. No dosage adjustment is required for elderly patients. The mean plasma half-life of hydrochlorothiazide has been reported to be 5-15 hours.
Following oral or intravenous administration of 14C irbesartan, 80-85% of the circulating plasma radioactivity is unchanged irbesartan. Irbesartan is metabolised in the liver by glucuronide conjugation and oxidation. The major circulating metabolite is irbesartan glucuronide (approximately 6%). In vitro studies indicate that irbesartan is primarily oxidised by the cytochrome P450 enzyme CYP2C9; the CYP3A4 isoenzyme has a negligible effect. Irbesartan and its metabolites are eliminated both by the liver and by the kidneys. Following either oral or intravenous administration of 14C irbesartan, approximately 20% of the radioactivity is excreted in the urine and the remainder in the faeces. Less than 2% of the dose is excreted in the urine as unchanged irbesartan. Hydrochlorothiazide is not metabolized, but is rapidly excreted by the kidneys. At least 61% of an orally administered dose is excreted unchanged within 24 hours. Hydrochlorothiazide crosses the placental barrier, but does not cross the blood-brain barrier, and is excreted in breast milk.
Renal impairment: In patients with renal impairment or in patients undergoing hemodialysis, the pharmacokinetic parameters of irbesartan are not significantly altered.
Irbesartan is not removed by haemodialysis. It has been reported that the half-life of hydrochlorothiazide increased to 21 hours in patients with creatinine clearance < 20 ml/min.
Hepatic impairment: In patients with mild to moderate cirrhosis, the pharmacokinetics of irbesartan are not significantly altered. Studies in patients with severe hepatic impairment have not been conducted.
Indication
Treatment of essential hypertension.
This fixed-dose combination is indicated in adult patients whose blood pressure is not adequately controlled on irbesartan or hydrochlorothiazide alone.
Contraindication
Hypersensitivity to the active substances or to any of the excipients, or to any substances that are derivatives of sulfonamides (hydrochlorothiazide is a sulfonamide derivative).
Severe renal failure (creatinine clearance < 30 ml/min).
Persistent form of hypokalemia, hypercalcemia.
Severe liver failure, cirrhosis and cholestasis.
Concomitant use of Co-Irbesartan® with aliskiren-containing drugs in patients with diabetes and patients with moderate to severe renal impairment (glomerular filtration rate < 60 ml/min/1.73 m2).
Concomitant use of Co-Irbesartan® with angiotensin-converting enzyme (ACE) inhibitors in patients with diabetic nephropathy.
Treatment-resistant hypokalemia or hypercalcemia.
Refractory hyponatremia.
Symptomatic hyperuricemia (gout).
Anury.
Pregnancy and breastfeeding.
Childhood.
Interaction with other medicinal products and other types of interactions
Other antihypertensive drugs. The antihypertensive effect of Co-Irbesartan® may be enhanced by the concomitant use of other antihypertensive drugs. Irbesartan and hydrochlorothiazide (in doses up to 300 mg irbesartan/25 mg hydrochlorothiazide) have been safely administered with other antihypertensive drugs, including calcium channel blockers and β-blockers. Previous treatment with high doses of diuretics may result in volume depletion and a risk of decreased blood pressure when irbesartan is started with thiazide diuretics, unless volume depletion has been corrected.
Lithium preparations. Transient increases in serum lithium concentrations and toxicity have been reported during concomitant use of lithium with angiotensin-converting enzyme inhibitors. Very rare cases of similar effects have been reported with irbesartan to date. In addition, thiazides reduce the renal excretion of lithium, so the risk of lithium toxicity may increase when using Co-Irbesan®. Therefore, the combination of lithium and Co-Irbesan® is not recommended (see section "Special warnings and precautions for use"). If such a combination proves necessary, careful monitoring of serum lithium levels is recommended.
Potassium-sparing medicinal products. The potassium-sparing effect of hydrochlorothiazide is attenuated by the potassium-sparing effect of irbesartan. However, it is believed that this effect of hydrochlorothiazide on serum potassium levels may be mediated by other medicinal products associated with potassium loss and hypokalaemia (e.g. other potassium-sparing diuretics, laxatives, amphotericin, carbenoxolone, penicillin G sodium). Conversely, based on experience with other medicinal products that inhibit the renin-angiotensin system, concomitant use of non-potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes or other medicinal products that may increase serum potassium levels (e.g. heparin sodium) may lead to increases in serum potassium levels. Appropriate monitoring of serum potassium levels is recommended in patients at risk.
Medicinal products affected by serum potassium disturbances. Periodic monitoring of serum potassium is recommended if Co-Irbesartan® is used concomitantly with medicinal products whose toxicity is increased by serum potassium disturbances (e.g. digitalis glycosides, antiarrhythmics).
ACE inhibitors. The concomitant use of Co-Irbesartan® with ACE inhibitors is contraindicated in patients with diabetic nephropathy and is not recommended for all other patients.
Non-steroidal anti-inflammatory drugs (NSAIDs): When angiotensin II antagonists are used concomitantly with NSAIDs (i.e. selective COX-2 inhibitors, acetylsalicylic acid (> 3 g/day) and non-selective non-steroidal anti-inflammatory drugs), attenuation of the antihypertensive effect may occur.
As with ACE inhibitors, concomitant use of angiotensin II antagonists and NSAIDs may lead to an increased risk of worsening of renal function, including possible acute renal failure and increases in serum potassium, especially in patients with pre-existing poor renal function. The combination should be used with caution, especially in the elderly. Patients should be adequately hydrated and attention should be paid to monitoring renal function after initiation of such combination therapy and periodically thereafter.
Additional information on irbesartan interactions. Studies have shown that the pharmacokinetics of irbesartan are not affected by hydrochlorothiazide. Irbesartan is mainly eliminated by CYP2C9 and to a lesser extent by glucuronidation. No significant pharmacokinetic or pharmacodynamic interactions were observed when irbesartan was administered with warfarin, a drug metabolized by CYP2C9. The effect of CYP2C9 inducers such as rifampicin on the pharmacokinetics of irbesartan has not been determined. The pharmacokinetics of digoxin were not altered by concomitant administration of irbesartan.
Potassium supplements and potassium-sparing diuretics: Based on experience with other medicinal products that affect the renin-angiotensin system, the concomitant use of potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes or other medicinal products that may increase serum potassium levels (e.g. heparin) may lead to increases in serum potassium levels and is therefore not recommended.
Additional information on hydrochlorothiazide interactions: When used concomitantly with thiazide diuretics, interactions with the following drugs are possible.
Alcohol: May cause orthostatic hypotension.
Antidiabetic drugs (oral agents and insulins): Dosage adjustment of the antidiabetic drug may be required.
Metformin should be used with caution due to the risk of lactic acidosis due to possible hydrochlorothiazide-induced functional renal failure.
Cholestyramine and colestipol resins. In the presence of anion exchange resins, the absorption of hydrochlorothiazide is impaired. Co-Irbesartan® should be taken at least 1 hour before or 4 hours after taking these drugs.
Corticosteroids, ACTH: Electrolyte depletion, especially hypokalemia may be exacerbated.
Digitalis glycosides: Thiazide-induced hypokalemia or hypomagnesemia contributes to the development of digitalis glycoside-induced cardiac arrhythmias.
Pressor amines (e.g., norepinephrine). The effects of pressor amines may be reduced, but not enough to preclude their use.
Non-depolarizing muscle relaxants (e.g. tubocurarine): The effects of non-depolarizing muscle relaxants may be potentiated by hydrochlorothiazide.
Gout medications. Dosage adjustment of gout medications may be necessary since hydrochlorothiazide may increase serum uric acid levels. Dosage of probenecid or sulfinpyrazone may need to be increased. Concomitant use of thiazide diuretics may increase the incidence of hypersensitivity reactions to allopurinol.
Calcium salts: Thiazide diuretics may increase serum calcium levels due to decreased excretion. If calcium supplements or drugs that do not excrete calcium (e.g. vitamin D) are required, serum calcium levels should be monitored and calcium dosage adjusted accordingly.
Carbamazepine: Concomitant use of carbamazepine and hydrochlorothiazide has been associated with a risk of symptomatic hyponatremia. Electrolyte levels should be monitored when these drugs are used concomitantly. If possible, a different class of diuretic should be used.
Drugs whose effects are affected by changes in serum potassium levels:
Periodic monitoring of serum potassium and ECG is recommended if hydrochlorothiazide is taken concomitantly with drugs whose effects are affected by changes in serum potassium (such as digitalis glycosides and antiarrhythmic drugs) and the following drugs that induce torsades de pointes (including some antiarrhythmic drugs), since hypokalemia is a factor contributing to the development of torsades de pointes:
Class Ia antiarrhythmics (e.g. quinidine, hydroquinidine, disopyramide);
class III antiarrhythmics (e.g. amiodarone, sotalol, dofetilide, ibutilide);
some neuroleptics (e.g. thioridazine, chlorpromazine, levomepromazine, trifluoroperazine, cyamemazine, sulpiride, sultopride, amisulpiride, tiapride, pimozide, haloperidol, droperidol);
other medicines (e.g. bepridil, cisapride, diphemanil, intravenous erythromycin, halofantrine, mizolastine, pentamidine, terfenadine, intravenous vincamine).
Methyldopa: Isolated cases of hemolytic anemia have been reported with concomitant use of hydrochlorothiazide and methyldopa.
Salicylates: When using high doses of salicylates, hydrochlorothiazide may enhance their toxic effects on the central nervous system.
Cyclosporine: Concomitant use of cyclosporine may increase hyperuricemia and increase the risk of gout-like complications.
Alcohol, barbiturates, narcotics, or antidepressants. May increase orthostatic hypotension.
β-Blockers and Diaxoside. Concomitant use of thiazide diuretics, including hydrochlorothiazide, with β-blockers may increase the risk of hyperglycemia. Thiazide diuretics, including hydrochlorothiazide, may potentiate the hyperglycemic effect of Diaxoside.
Amantadine: Thiazides, including hydrochlorothiazide, may increase the risk of side effects caused by amantadine.
Effect of drugs on laboratory test results: Due to their effect on calcium metabolism, thiazides may interfere with the results of parathyroid function tests.
Specific hyposensitization. ACE inhibition increases the likelihood and severity of anaphylactic and anaphylactoid reactions to insect venom. It is believed that this effect may also be observed for other allergens.
Iodinated contrast media: In the case of diuretic-induced dehydration, the risk of acute renal failure is increased, especially with high doses of iodinated contrast media. Patients should be rehydrated before administration of iodinated contrast media.
Amphotericin B (for parenteral administration), corticosteroids, ACTH and stimulant laxatives. Hydrochlorothiazide increases electrolyte imbalance, mainly hypokalemia.
Other forms of interaction: The hyperglycemic effect of β-blockers and diazoxide may be potentiated by thiazides.
Anticholinergic agents (e.g. atropine, biperiden) may increase the bioavailability of thiazide-type diuretics by reducing gastrointestinal tone and gastric emptying rate.
Thiazides may increase the risk of adverse effects caused by amantadine. Thiazides may reduce the renal excretion of cytotoxic drugs (e.g. cyclophosphamide, methotrexate) and enhance their bone marrow suppressive effects.
Application features
Decreased blood pressure - patients with low blood volume. Co-Irbesartan® is rarely associated with symptomatic hypotension in hypertensive patients without other risk factors for hypotension. Symptomatic hypotension may occur in patients who are volume and/or sodium depleted by intensive diuretic therapy, dietary salt restriction, diarrhea, or vomiting. These conditions should be corrected before initiating treatment with Co-Irbesartan®.
Patients with hypertension, type 2 diabetes and chronic kidney disease. The effects of irbesartan on renal and cardiovascular function were not consistent across subgroups analyzed in a study of patients with end-stage chronic kidney disease. In particular, the benefits were less pronounced in women and in non-Caucasian subjects.
Renal artery stenosis - renovascular hypertension: There is an increased risk of severe hypotension and renal failure when patients with bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney are treated with ACE inhibitors or angiotensin II receptor antagonists. If this is not observed with Co-Irbesartan®, a similar effect should be expected.
Renal impairment and kidney transplantation. If Co-Irbesartan® is used in patients with impaired renal function, periodic monitoring of serum calcium, creatinine and uric acid is recommended. There is no experience with the use of Co-Irbesartan® in patients who have recently undergone kidney transplantation. Co-Irbesartan® should not be used in patients with severe renal impairment (creatinine clearance < 30 ml/min). Patients with impaired renal function may develop azotemia associated with thiazide diuretics. No dosage adjustment is required for patients with renal impairment with creatinine clearance ≥ 30 ml/min. However, this fixed-dose combination should be used with caution in patients with mild to moderate renal impairment (creatinine clearance ≥ 30 ml/min but < 60 ml/min).
Dual blockade of the renin-angiotensin-aldosterone system (RAAS). Dual blockade of the RAAS by combining Co-Irbesartan® with aliskiren is not recommended due to the increased risk of hypotension, hyperkalemia and changes in renal function. The simultaneous use of Co-Irbesartan® with aliskiren-containing drugs is contraindicated in patients with diabetes and in patients with moderate to severe renal impairment (glomerular filtration rate < 60 ml/min/1.73 m2).
Hepatic impairment: Thiazides should be used with caution in patients with impaired hepatic function or progressive liver disease, since minor changes in fluid and electrolyte balance may precipitate hepatic coma. There is no clinical experience with Co-Irbesartan® in patients with hepatic impairment.
Thiazides should be used with caution in hepatic disorders and progressive liver disease, as these drugs can cause intrahepatic cholestasis, and even minimal changes in water-salt balance can provoke the development of hepatic coma. Hydrochlorothiazide is contraindicated in patients with severe hepatic insufficiency.
Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy: As with other vasodilators, special precautions should be taken in patients suffering from aortic or mitral valve stenosis or obstructive hypertrophic cardiomyopathy.
Primary aldosteronism. Patients with primary aldosteronism usually do not have a hypotensive effect when using agents that act by inhibiting the renin-angiotensin system, therefore the use of Co-Irbesartan® is not recommended.
Effects on metabolism and endocrine system. During thiazide diuretic therapy, glucose tolerance may be impaired. There is a need to adjust the dosage of insulin or oral hypoglycemic drugs for patients with diabetes. During thiazide diuretic therapy, signs of diabetes mellitus that was in a latent stage may appear.
Elevations in cholesterol and triglyceride levels have been associated with thiazide diuretic therapy; however, minimal or no effect has been reported at the 12.5 mg dose contained in Co-Irbesartan®.
Some patients who are to receive thiazide diuretic therapy may develop hyperuricemia or develop signs of gout.
Thiazides, including hydrochlorothiazide, may cause fluid or electrolyte imbalance (hypokalemia, hyponatremia, and hypochloraemic alkalosis). Typical signs of fluid or electrolyte imbalance to look out for include dry mouth, thirst, weakness, fatigue, drowsiness, restlessness, muscle pain or cramps, muscular weakness, decreased blood pressure, oliguria, tachycardia, and gastrointestinal disturbances such as nausea or vomiting.
Although hypokalemia may occur with thiazide diuretics, concomitant therapy with irbesartan may attenuate the hypokalemia that occurs with diuretics. The highest risk of hypokalemia is in patients with cirrhosis of the liver, in patients with vigorous diuresis, in patients receiving inadequate oral electrolytes, and in patients receiving concomitant treatment with corticosteroids or ACTH. Conversely, hyperkalemia may occur due to the presence of irbesartan in Co-Irbesartan®, especially in the presence of renal insufficiency and/or heart failure, as well as diabetes mellitus. Appropriate monitoring of serum potassium is recommended in patients at risk. Potassium-sparing diuretics, potassium supplements, or potassium-containing salt substitutes should be used with caution with Co-Irbesartan®.
There is no evidence that irbesartan can attenuate or prevent diuretic-induced hyponatremia. Chloride deficiency is generally mild and usually does not require treatment.
Thiazides may reduce urinary calcium excretion and cause a transient and minor increase in serum calcium in the absence of known disorders of calcium metabolism. Marked hypercalcemia may indicate latent hyperparathyroidism. Thiazides should be discontinued before parathyroid function tests are performed.
Thiazides have been shown to increase urinary magnesium excretion, which may lead to hypomagnesemia.
Lithium preparations. It is not recommended to use lithium preparations and Co-Irbesartan® simultaneously.
Anti-doping control: Hydrochlorothiazide, which is contained in this medicinal product, may give a positive analytical result during anti-doping control.
General precautions: In patients whose vascular tone and renal function depend predominantly on the activity of the renin-angiotensin-aldosterone system (e.g. patients with severe congestive heart failure or underlying renal disease, including renal artery stenosis), treatment with ACE inhibitors or angiotensin II receptor antagonists that affect this system has been associated with acute hypotension, azotemia, oliguria or, rarely, acute renal failure. As with any antihypertensive agent, excessive reduction in blood pressure in patients with ischaemic cardiopathy or ischaemic cardiovascular disease could result in myocardial infarction or stroke. Hypersensitivity reactions to hydrochlorothiazide may occur in patients with or without a history of allergy or bronchial asthma, but are more likely to occur in patients with a history of such conditions. Exacerbation or activation of systemic lupus erythematosus has been reported with the use of thiazide diuretics.
Photosensitivity reactions have been reported with thiazide diuretics. If a photosensitivity reaction occurs during treatment, it is recommended to discontinue treatment. If repeated use of such diuretics is considered necessary, it is recommended to protect exposed areas of the body from sunlight or artificial UVA radiation.
Acute myopia and secondary acute angle-closure glaucoma. Medicinal products containing sulfonamides or their derivatives may cause idiosyncrasies leading to transient myopia and acute angle-closure glaucoma. Hydrochlorothiazide is a sulfonamide derivative, but only isolated cases of acute angle-closure glaucoma have been reported with hydrochlorothiazide. Symptoms of this condition include acute visual impairment or eye pain. These symptoms usually develop within hours to weeks of initiating therapy with this drug. If acute angle-closure glaucoma is left untreated, it may lead to irreversible vision loss in the patient. If such a symptom occurs, the first step should be to discontinue therapy with this drug as soon as possible. If intraocular pressure remains uncontrolled after this, medical or surgical treatment may be considered. Risk factors for developing acute angle-closure glaucoma may include a history of allergy to sulfonamide or penicillin.
Acute respiratory toxicity
Very rare cases of severe acute respiratory toxicity, including ARDS, have been reported following the administration of hydrochlorothiazide. Pulmonary edema usually develops within minutes to hours after administration of hydrochlorothiazide. Early symptoms include dyspnea,
