Valsartan HCT Stada

Valsartan, hydrochlorothiazide.

Each tablet contains 80 mg of valsartan and 12.5 mg of hydrochlorothiazide.
Excipients/Inactive Ingredients: Lactose monohydrate, Cellulose, Hypromellose, Croscarmellose sodium, Colloidal anhydrous silica, Magnesium Stearate, Macrogol, Talc, Titanium dioxide, Iron Oxide Red (E172).
The film-coated tablets must not be divided.

Pharmacotherapeutic group: Angiotensin II antagonists and diuretics, valsartan and diuretics. ATC code: C09D A03.
Pharmacology: Pharmacodynamics: Valsartan: Valsartan is an orally active and specific angiotensin II (Ang II) receptor antagonist. It acts selectively on the AT₁ receptor subtype, which is responsible for the known actions of angiotensin II. The increased plasma levels of Ang II following AT₁ receptor blockade with valsartan may stimulate the unblocked AT₂ receptor, which appears to counterbalance the effect of the AT₁ receptor. Valsartan does not exhibit any partial agonist activity at the AT₁ receptor and has much (about 20,000-fold) greater affinity for the AT₁ receptor than for the AT₂ receptor. Valsartan is not known to bind to or block other hormone receptors or ion channels known to be important in cardiovascular regulation.
Valsartan does not inhibit ACE, also known as kininase II, which converts Ang I to Ang II and degrades bradykinin. Since there is no effect on ACE and no potentiation of bradykinin or substance P, angiotensin II antagonists are unlikely to be associated with coughing.
Administration of valsartan to patients with hypertension results in reduction of blood pressure without affecting pulse rate. In most patients, after administration of a single oral dose, onset of antihypertensive activity occurs within 2 hours, and the peak reduction of blood pressure is achieved within 4-6 hours. The antihypertensive effect persists over 24 hours after dosing. During repeated dosing, the maximum reduction in blood pressure with any dose is generally attained within 2-4 weeks and is sustained during long-term therapy. Combined with hydrochlo­rothiazide, a significant additional reduction in blood pressure is achieved.
Abrupt withdrawal of valsartan has not been associated with rebound hypertension or other adverse clinical events.
In hypertensive patients with type 2 diabetes and microalbuminuria, valsartan has been shown to reduce the urinary excretion of albumin.
Hydrochlorothiazide: The site of action of thiazide diuretics is primarily in the renal distal convoluted tubule. It has been shown that there is a high-affinity receptor in the renal cortex as the primary binding site for the thiazide diuretic action and inhibition of NaCl transport in the distal convoluted tubule. The mode of action of thiazides is through inhibition oft he Na⁺Cl^- symporter perhaps by competing for the Cl^- site, thereby affecting electrolyte reabsorption mechanisms: directly increasing sodium and chloride excretion to an approximately equal extent, and indirectly by this diuretic action reducing plasma volume, with consequent increases in plasma renin activity, aldosterone secretion and urinary potassium loss, and a decrease in serum potassium.
The renin-aldosterone link is mediated by angiotensin II, so with co-administration of valsartan the reduction in serum potassium is less pronounced as observed under monotherapy with hydrochlorothiazide.
Pharmacokinetics: Valsartan/hydrochlorothiazide: The systemic availability of hydrochlorothiazide is reduced by about 30% when co-administered with valsartan. The kinetics of valsartan are not markedly affected by the co-administration of hydrochlorothiazide. This observed interaction has no impact on the combined use of valsartan and hydrochlorothiazide, since controlled clinical trials have shown a clear anti-hypertensive effect, greater than that obtained with either active substance given alone, or placebo.
Valsartan: Absorption: Following oral administration of valsartan alone, peak plasma concentrations of valsartan are reached in 2-4 hours. Mean absolute bioavailability is 23%. Food decreases exposure (as measured by AUC) to valsartan by about 40% and peak plasma concentration (C_max) by about 50%, although from about 8 h post dosing plasma valsartan concentrations are similar for the fed and fasted groups. This reduction in AUC is not, however, accompanied by a clinically significant reduction in the therapeutic effect, and valsartan can therefore be given either with or without food.
Distribution: The steady-state volume of distribution of valsartan after intravenous administration is about 17 litres, indicating that valsartan does not distribute into tissues extensively. Valsartan is highly bound to serum proteins (94-97%), mainly serum albumin.
Biotransformation: Valsartan is not biotransformed to a high extent as only about 20% of dose is recovered as metabolites. A hydroxy metabolite has been identified in plasma at low concentrations (less than 10% of the valsartan AUC). This metabolite is pharmacologically inactive.
Elimination: Valsartan shows multiexponential decay kinetics (t½α <1 h and t½β about 9 h). Valsartan is primarily eliminated in faeces (about 83% of dose) and urine (about 13% of dose), mainly as unchanged drug. Following intravenous administration, plasma clearance of valsartan is about 2 l/h and its renal clearance is 0.62 l/h (about 30% of total clearance). The half-life of valsartan is 6 hours.
Hydrochlorothiazide: Absorption: The absorption of hydrochlorothiazide, after an oral dose, is rapid (t_max about 2 h), with similar absorption characteristics for both suspension and tablet formulations. Absolute bioavailability of hydrochlorothiazide is 60-80% after oral administration. Concomitant administration with food has been reported to both increase and decrease the systemic availability of hydrochlorothiazide compared with the fasted state. The magnitude of these effects is small and has minimal clinical importance. The increase in mean AUC is linear and dose proportional in the therapeutic range. There is no change in the kinetics of hydrochlorothiazide on repeated dosing, and accumulation is minimal when dosed once daily.
Distribution: The distribution and elimination kinetics have generally been described by a bi-exponential decay function.
The apparent volume of distribution is 4-8 l/kg.
Circulating hydrochlorothiazide is bound to serum proteins (40-70%), mainly serum albumin.
Hydrochlorothiazide also accumulates in erythrocytes at approximately 1.8 times the level in plasma.
Elimination: For hydrochlorothiazide, >95% of the absorbed dose being excreted as unchanged compound in the urine. The renal clearance is composed of passive filtration and active secretion into the renal tubule. The terminal half-life is 6-15 h.
Special populations: Elderly: A somewhat higher systemic exposure to valsartan was observed in some elderly subjects than in young subjects; however, this has not been shown to have any clinical significance. Limited data suggest that the systemic clearance of hydrochlorothiazide is reduced in both healthy and hypertensive elderly subjects compared to young healthy volunteers.
Renal impairment: At the recommended dose of Valsartan HCT, no dose adjustment is required for patients with a creatinine clearance of 30-70 ml/min.
In patients with severe renal impairment (creatinine clearance <30 ml/min) and patients undergoing dialysis no data are available for Valsartan HCT. Valsartan is highly bound to plasma protein and is not to be removed by dialysis, whereas clearance of hydrochlorothiazide will be achieved by dialysis.
Renal clearance of hydrochlorothiazide is composed of passive filtration and active secretion into the renal tubule. As expected for a compound which is cleared almost exclusively via the kidneys, renal function has a marked effect on the kinetics of hydrochlorothiazide (see Contraindications).
Hepatic impairment: In a pharmacokinetics trial in patients with mild (n=6) to moderate (n=5) hepatic dysfunction, exposure to valsartan was increased approximately 2-fold compared with healthy volunteers. There is no data available on the use of valsartan in patients with severe hepatic dysfunction (see Contraindications). Hepatic disease does not significantly affect the pharmacokinetics of hydrochlorothiazide.

Treatment of essential hypertension in adults.
Valsartan HCT fixed-dose combination is indicated in patients whose blood pressure is not adequately controlled on valsartan or hydrochlorothiazide monotherapy.

Posology: The recommended dose of Valsartan HCT is one film-coated tablet once daily. Dose titration with the individual components is recommended. In each case, up-titration of individual components to the next dose should be followed in order to reduce the risk of hypotension and other adverse events.
When clinically appropriate direct change from monotherapy to the fixed combination may be considered in patients whose blood pressure is not adequately controlled on valsartan or hydrochlorothiazide monotherapy, provided the recommended dose titration sequence for the individual components is followed.
The clinical response to Valsartan HCT should be evaluated after initiating therapy and if blood pressure remains uncontrolled, the dose may be increased by increasing either one of the components to a maximum dose of Valsartan HCT 320 mg/25 mg.
The antihypertensive effect is substantially present within 2 weeks.
In most patients, maximal effects are observed within 4 weeks. However, in some patients, 4-8 weeks treatment may be required. This should be taken into account during dose-titration.
Method of administration: Valsartan HCT can be taken with or without food and should be administered with water.
Special populations: Renal impairment: No dose adjustment is required for patients with mild to moderate renal impairment (creatinine clearance ≥30 ml/min). Due to the hydrochlorothiazide component, Valsartan HCT is contraindicated in patients with severe renal impairment (see Contraindications, Precautions and Pharmacology: Pharmacokinetics under Actions).
Hepatic impairment: In patients with mild to moderate hepatic impairment without cholestasis the dose of valsartan should not exceed 80 mg (see Precautions). Valsartan HCT is contraindicated in patients with severe hepatic impairment (see Contraindications, Precautions and Pharmacology: Pharmacokinetics under Actions).
Elderly: No dose adjustment is required in elderly patients.
Paediatric patients: Valsartan HCT is not recommended for use in children below the age of 18 years due to a lack of data on safety and efficacy.

Symptoms: Overdose with valsartan may result in marked hypotension, which could lead to depressed level of consciousness, circulatory collapse and/or shock. In addition, the following signs and symptoms may occur due to an overdose of the hydrochlorothiazide component: nausea, somnolence, hypovolaemia, and electrolyte disturbances associated with cardiac arrhythmias and muscle spasms.
Treatment: The therapeutic measures depend on the time of ingestion and the type and severity of the symptoms, stabilisation of the circulatory condition being of prime importance.
If hypotension occurs, the patient should be placed in the supine position and salt and volume supplementation should be given rapidly.
Valsartan cannot be eliminated by means of haemodialysis because of its strong plasma binding behaviour whereas clearance of hydrochlorothiazide will be achieved by dialysis.

Hypersensitivity to valsartan, hydrochlorothiazide, other sulfonamide-derived medicinal products or to any of the excipients.
Second and third trimester of pregnancy (see Precautions and Use in Pregnancy & Lactation).
Severe hepatic impairment, biliary cirrhosis and cholestasis.
Severe renal impairment (creatinine clearance <30 ml/min, anuria.
Refractory hypokalaemia, hyponatraemia, hypercalcaemia, and symptomatic hyperuricaemia.
The concomitant use of Valsartan HCT with aliskiren-containing products is contraindicated in patients with diabetes mellitus or renal impairment (GFR <60 ml/min/1.73 m²).

Dual blockade of the renin-angiotensin-aldosterone system (RAAS): There is evidence that the concomitant use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of hypotension, hyperalaemia and decreased renal function (including acute renal failure). Dual blockade of RAAS through the combined use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren is therefore not recommended. If dual blockade therapy is considered absolutely necessary, this should only occur under specialist supervision and subject to frequent close monitoring of renal function, electrolytes and blood pressure. ACE-inhibitors and angiotensin II receptor blockers should not be used concomitantly in patients with diabetic nephropathy.
Serum electrolyte changes: Valsartan: Concomitant use with potassium supplements, potassium-sparing diuretics, salt substitutes containing potassium, or other agents that may increase potassium levels (heparin etc.) is not recommended.
Monitoring of potassium should be undertaken as appropriate.
Hydrochlorothiazide: Hypokalaemia has been reported under treatment with thiazide diuretics, including hydrochlorothiazide. Frequent monitoring of serum potassium is recommended.
Treatment with thiazide diuretics, including hydrochlorothiazide, has been associated with hyponatraemia and hypochloraemic alkalosis. Thiazides, including hychlorothiazide, increase the urinary excretion of magnesium, which may result in hypomagnesaemia. Calcium excretion is decreased by thiazide diuretics. This may result in hypercalcaemia.
As of any patient receiving diuretic therapy, periodic determination of serum electrolytes should be performed at appropriate intervals.
Sodium and/or volume-depleted patients: Patients receiving thiazide diuretics, including hydrochlorothiazide, should be observed for clinical signs of fluid or electrolyte imbalance.
In severely sodium-depleted and/or volume-depleted patients, such as those receiving high doses of diuretics, symptomatic hypotension may occur in rare cases after initiation of therapy with Valsartan HCT. Sodium and/or volume depletion should be corrected before starting treatment with Valsartan HCT.
Patients with severe chronic heart failure or other conditions with stimulation of the renin-angiotensin-aldosterone-system: In patients whose renal function may depend on the activity of the renin-angiotensin-aldosterone system (e.g. patients with severe congestive heart failure), treatment with angiotensin converting enzyme inhibitors has been associated with oliguria and/or progressive azotaemia, and in rare cases with acute renal failure. The use of Valsartan HCT in patients with severe chronic heart failure has not been established.
Hence, it cannot be excluded that because of the inhibition of the renin-angiotensin-aldosterone system the application of Valsartan HCT as well may be associated with impairment of the renal function. Valsartan HCT should not be used in these patients.
Renal artery stenosis: Valsartan HCT should not be used to treat hypertension in patients with unilateral or bilateral renal artery stenosis or stenosis of the artery to a solitary kidney, since blood urea and serum creatinine may increase in such patients.
Primary hyperaldosteronism: Patients with primary hyperaldosteronism should not be treated with Valsartan HCT as their renin-angiotensin system is not activated.
Aortic and mitral valve stenosis, hypertrophic obstructive cardiomyopathy: As with all other vasodilators, special caution is indicated in patients suffering from aortic or mitral stenosis, or hypertrophic obstructive cardiomyopathy (HOCM).
Renal impairment: No dosage adjustment is required for patients with renal impairment with a creatinine clearance ≥30 ml/min (see Dosage & Administration). Periodic monitoring of serum potassium, creatinine and uric acid levels is recommended when Valsartan HCT is used in patients with renal impairment.
Kidney transplantation: There is currently no experience on the safe use of Valsartan HCT in patients who have recently undergone kidney transplantation.
Hepatic impairment: In patients with mild to moderate hepatic impairment without cholestasis, Valsartan HCT should be used with caution (see Dosage & Administration and Pharmacology: Pharmacokinetics under Actions).
Systemic lupus erythematosus: Thiazide diuretics, including hydrochlorothiazide, have been reported to exacerbate or activate systemic lupus erythematosus.
Other metabolic disturbances: Thiazide diuretics, including hydrochlorothiazide, may alter glucose tolerance and raise serum levels of cholesterol, triglycerides and uric acid. In diabetic patients dosage adjustments of insulin or oral hypoglycaemic agents may be required.
Thiazides may reduce urinary calcium excretion and cause an intermittent and slight elevation of serum calcium in the absence of known disorders of calcium metabolism. Marked hypercalcaemia may be evidence of underlying hyperparathyroidism. Thiazides should be discontinued before carrying out tests for parathyroid function.
Photosensitivity: Cases of photosensitivity reactions have been reported with thiazides diuretics (see Adverse Reactions). If photosensitivity reaction occurs during treatment, it is recommended to stop the treatment. If a re-administration of the diuretic is deemed necessary, it is recommended to protect exposed areas to the sun or to artificial UVA.
General: Caution should be exercised in patients who have shown prior hypersensitivity to other angiotensin II receptor antagonists. Hypersensitivity reactions to hydrochlorothiazide are more likely in patients with allergy and asthma.
Excipient: This medicinal product contains lactose monohydrate.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Effects on ability to drive and use machines: No studies on the effect of Valsartan HCT, on the ability to drive and use machines have been performed. When driving vehicles or operating machines it should be taken into account that occasionally dizziness or weariness may occur.
Use in Pregnancy: Angiotensin II Receptor Antagonists (AIIRAs) should not be initiated during pregnancy. Unless continued AIIRAs 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, treatment with AIIRAs should be stopped immediately, and, if appropriate, alternative therapy should be started (see Contraindications and Use in Pregnancy & Lactation).

Pregnancy: Valsartan: The use of Angiotensin II Receptor Antagonists (AIIRAs) is not recommended during first trimester of pregnancy (see Precautions). The use of AIIRAs is contra-indicated during the second and third trimester of pregnancy (see Contraindications and Precautions).
Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors during the first trimester of pregnancy has not been conclusive; however a small increase in risk cannot be excluded. Whilst there is no controlled epidemiological data on the risk with Angiotensin II Receptor Inhibitors (AIIRAs), similar risks may exist for this class of drugs. Unless continued AIIRAs therapy is considered essential, patients planning pregnancy should be changed to alternative anti-hypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with AIIRAs should be stopped immediately and, if appropriate, alternative therapy should be started.
AIIRAs therapy exposure during the second and third trimesters is known to induce human fetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalaemia).
Should exposure to AIIRAs have occurred from the second trimester of pregnancy, ultrasound check of renal function and skull is recommended.
Infants whose mothers have taken AIIRAs should be closely observed for hypotension (see also Contraindications and Precautions).
Hydrochlorothiazide: There is limited experience with hydrochlorothiazide during pregnancy, especially during the first trimester. Animal studies are insufficient. Hydrochlorothiazide crosses the placenta. Based on the pharmacological mechanism of action of hydrochlorothiazide its use during the second and third trimester may compromise feto-placental perfusion and may cause foetal and neonatal effects like icterus, disturbance of electrolyte balance and thrombocytopenia.
Hydrochlorothiazide should not be used for gestational oedema, gestational hypertension or preeclampsia due to the risk of decreased plasma volume and placental hypoperfusion, without a beneficial effect on the course of the disease.
Hydrochlorothiazide should not be used for essential hypertension in pregnant women except in rare situations where no other treatment could be used.
Lactation: No information is available regarding the use of valsartan during breastfeeding. Hydrochlorothiazide is excreted in human milk. Therefore the use of Valsartan HCT during breast feeding is not recommended.
Alternative treatments with better established safety profiles during breast-feeding are preferable, especially while nursing a newborn or preterm infant.

Adverse reactions reported in clinical trials and laboratory findings occurring more frequently with valsartan plus hydrochlorothiazide versus placebo and individual postmarketing reports are presented below according to system organ class. Adverse reactions known to occur with each component given individually but which have not been seen in clinical trials may occur during treatment with valsartan/hydrochlorothiazide.
Adverse drug reactions are ranked by frequency, the most frequent first, using the following convention: 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). Within each frequency grouping, adverse reactions are ranked in order of decreasing seriousness. (See Table 1.)

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Additional information on the individual components: Adverse reactions previously reported with one of the individual components may be potential undesirable effects with Valsartan HCT as well, even if not observed in clinical trials or during postmarketing period. (See Tables 2 and 3.)

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Click on icon to see table/diagram/image

Clinical Trial data has shown that dual blockade of renin-angiotensin-aldosterone system (RAAS) through the combined use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren is associated with a higher frequency of adverse events such as hypotension, hyperkalaemia and decresed renal function (including acute renal failure) compared to the use of single RAAS-acting agent.
Interactions related to both valsartan and hydrochlorothiazide: Concomitant use not recommended: Lithium: Reversible increases in serum lithium concentrations and toxicity have been reported during concurrent use of ACE inhibitors and thiazide, including hydrochlorothiazide. Due to the lack of experience with concomitant use of valsartan and lithium, this combination is not recommended. If the combination proves necessary, careful monitoring of serum lithium levels is recommended.
Concomitant use requiring caution: Other antihypertensive agents: Valsartan HCT may increase the effects of other agents with antihypertensive properties (e.g. ACEI, beta-blockers, calcium channel blockers).
Pressor amines (e.g. noradrenaline, adrenaline): Possible decreased response to pressor amines but not sufficient to preclude their use.
Non-steroidal anti-inflammatory medicines (NSAIDs), including selective COX-2 inhibitors, acetylsalicylic acid >3 g/day), and non-selective NSAIDs: NSAIDs can attenuate the antihypertensive effect of both angiotensin II antagonists and hydrochlorothiazide when administered simultaneously. Furthermore, concomitant use of Valsartan HCT and NSAIDs may lead to worsening of renal function and an increase in serum potassium. Therefore, monitoring of renal function at the beginning of the treatment is recommended, as well as adequate hydration of the patient.
Interactions related to valsartan: Concomitant use not recommended: Potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium and other substances that may increase potassium levels: If a medicinal product that affects potassium levels is considered necessary in combination with valsartan, monitoring of potassium plasma levels is advised.
No interaction: In drug interaction studies with valsartan, no interactions of clinical significance have been found with valsartan or any of the following substances: cimetidine, warfarin, furosemide, digoxin, atenolol, indomethacin, hydrochlorothiazide, amlodipine, glibenclamide. Digoxin and indomethacin could interact with the hydrochlorothiazide component of Valsartan HCT (see Interactions related to hydrochlorothiazide).
Interactions related to hydrochlorothiazide: Concomitant use requiring caution: Medicinal products associated with potassium loss and hypokalaemia (e.g. kaliuretic diuretics, corticosteroids, laxatives, ACTH, amphotericin, carbenoxolone, penicillin G, salicylic acid and derivatives): If these medicinal products are to be prescribed with the hydrochlorothiazide-valsartan combination, monitoring of potassium plasma levels is advised. These medicinal products may potentiate the effect of hydrochlorothiazide on serum potassium (see Precautions).
Medicinal products that could induce torsades de pointes: Class Ia antiarrhythmics (e.g. quinidine, hydroquinidine, disopyramide).
Class III antiarrhythmics (e.g. amiodarone, sotalol, dofetilide, ibutilide).
Some antipsychotics (e.g. thioridazine, chlorpromazine, levomepromazine, trifluoperazine, cyamemazine, sulpiride, sultopride, amisulpride, tiapride, pimozide, haloperidol, droperidol).
Others (e.g. bepridil, cisapride, diphemanil, erythromycin i.v., halofantrin, ketanserin, mizolastin, pentamidine, sparfloxacine, terfenadine, vincamine i.v.).
Due to the risk of hypokalemia, hydrochlorothiazide should be administered with caution when associated with medicinal products that could induce torsades de pointes.
Digitalis glycosides: Thiazide-induced hypokalaemia or hypomagnesaemia may occur as unwanted effects favouring the onset of digitalis-induced cardiac arrhythmias.
Calcium salts and vitamin D: Administration of thiazide diuretics, including hydrochlorothiazide, with vitamin D or with calcium salts may potentiate the rise in serum calcium.
Antidiabetic agents (oral agents and insulin): The treatment with a thiazide may influence the glucose tolerance. Dose adjustment of the antidiabetic medicinal product may be necessary.
Metformin should be used with caution because of the risk of lactic acidosis induced by possible functional renal failure linked to hydrochlorothiazide.
Beta blockers and diazoxide: Concomitant use of thiazide diuretics, including hydrochlorothiazide, with beta blockers may increase the risk of hyperglycaemia. Thiazide diuretics, including hydrochlorothiazide, may enhance the hyperglycaemic effect of diazoxide.
Medicinal products used in the treatment of gout (probenecid, sulfinpyrazone and allopurinol): Dose adjustment of uricosuric medications may be necessary as hydrochlorothiazide may raise the level of serum uric acid. Increase of dosage of probenecid or sulfinpyrazone may be necessary. Co-administration of thiazide diuretics, including hydrochlorothiazide, may increase the incidence of hypersensitivity reactions to allopurinol,
Anticholinergic agents (e.g. atropine, biperiden): The bioavailability of thiazide-type diuretics may be increased by anticholinergic agents, apparently due to a decrease in gastrointestinal motility and the stomach emptying rate.
Amantadine: Thiazides, including hydrochlorothiazide, may increase the risk of adverse effects caused by amantadine.
Cholestyramine and cholestipol resins: Absorption of thiazide diuretics, including hydrochlorothiazide, is impaired in the presence of anionic exchange resins.
Cytotoxic agents (e.g. cyclophosamide, methotrexate): Thiazides, including hydrochlorothiazide, may reduce renal excretion of cytotoxic agents and potentiate their myelosuppressive effects.
Non-depolarising skeletal muscle relaxants (e.g. tubocurarine): Thiazides, including hydrochlorothiazide, potentiate the action of curare derivatives.
Ciclosporin: Concomitant treatment with ciclosporin may increase the risk of hyperuricaemia and gout-type complications.
Alcohol, anaesthetics and sedatives: Potentiation of orthostatic hypotension may occur.
Methyldopa: There have been isolated reports of haemolytic anaemia in patients receiving concomitant treatment with methyldopa and hydrochlorothiazide.
Carbamazepine: Patients receiving hydrochlorothiazide concomitantly with carbamazepine may develop hyponatremia. Such patients should therefore be advised about the possibility of hyponatraemic reactions, and should be monitored accordingly.
Iodine contrast media: In case of diuretic-induced dehydration, there is an increased risk of acute renal failure, especially with high doses of the iodine product. Patients should be rehydrated before the administration.

Do not store above 25°C.
Shelf life: 3 years.

Angiotensin II Antagonists / Diuretics

C09DA03 - valsartan and diuretics ; Belongs to the class of angiotensin II receptor blockers (ARBs) in combination with diuretics. Used in the treatment of cardiovascular disease.

P₁S₁S₃