Instructions Diocor 80 film-coated tablets blister No. 30
Composition
active ingredients: valsartan, hydrochlorothiazide;
1 film-coated tablet contains:
80 mg of valsartan and 12.5 mg of hydrochlorothiazide (Diocor 80)
or 160 mg of valsartan and 12.5 mg of hydrochlorothiazide (Diocor 160);
excipients: microcrystalline cellulose, potato starch, corn starch, sodium lauryl sulfate, talc, croscarmellose sodium, colloidal anhydrous silica, magnesium stearate, coating for applying the shell Diokor 80 – Opadry II White (polyethylene glycol, polyvinyl alcohol, talc, titanium dioxide (E 171)); Diokor 160 – Opadry II Orange (talc, polyvinyl alcohol, quinoline yellow (E 104), polyethylene glycol, red iron oxide (E 172), yellow iron oxide (E 172), titanium dioxide (E 171)).
Dosage form
Film-coated tablets.
Main physicochemical properties:
Diocor 80 are round tablets with a biconvex surface, coated with a white film coating.
Diocor 160 are round tablets with a biconvex surface, coated with a brown-orange film coating.
Pharmacotherapeutic group
Combination drugs of angiotensin II inhibitors. Valsartan and diuretics.
ATX code C09D A03.
Pharmacological properties
Pharmacodynamics.
Diocor is an antihypertensive drug that contains an angiotensin II receptor antagonist and a thiazide diuretic.
The active hormone of the renin-angiotensin-aldosterone system is angiotensin II, formed from angiotensin I with the participation of angiotensin-converting enzyme (ACE).
Angiotensin II binds to specific receptors located on cell membranes in various tissues. It has a wide range of physiological actions, including both direct and indirect involvement in the regulation of blood pressure.
As a potent vasoconstrictor, angiotensin II exerts a direct vasopressor effect. In addition, it promotes sodium retention and stimulates aldosterone secretion.
Valsartan is a potent and specific angiotensin II receptor antagonist for oral administration. It acts selectively on the AT1 receptor subtype, which is responsible for the effects of angiotensin II. Increased levels of angiotensin II due to blockade of AT1 receptors by valsartan may stimulate free AT2 receptors, which balances the effect of AT1 receptors. Valsartan does not have any partial agonist activity at AT1 receptors and has a much higher (approximately 20,000-fold) affinity for AT1 receptors than for AT2 receptors.
Valsartan does not inhibit ACE (kininase II), which converts angiotensin I to angiotensin II and destroys bradykinin. No side effects caused by bradykinin have been observed.
In clinical trials comparing valsartan with an ACE inhibitor, the incidence of dry cough was significantly lower (P < 0.05) in patients treated with valsartan than in patients treated with an ACE inhibitor (2.6% versus 7.9%, respectively). It is known that patients previously treated with an ACE inhibitor develop dry cough, with valsartan reported in 19.5% of patients and thiazide diuretics in 19% of patients, while cough was reported in 68.5% of patients treated with an ACE inhibitor (P < 0.05). Valsartan does not interact with or block receptors for other hormones or ion channels that play an important role in the regulation of cardiovascular function.
In patients with hypertension, the drug causes a decrease in blood pressure without affecting the pulse rate.
In most patients, after a single dose of the drug, the onset of antihypertensive activity is noted within 2 hours, and the maximum reduction in blood pressure is achieved within 4-6 hours.
The antihypertensive effect persists for more than 24 hours after a single dose. With regular use of the drug, the maximum therapeutic effect is usually achieved within 2-4 weeks and is maintained at the achieved level during long-term therapy. When taking the combination with hydrochlorothiazide, a more effective reduction in blood pressure is observed.
Non-melanoma skin cancer: It is known that a cumulative dose-dependent relationship between hydrochlorothiazide use and the development of non-melanoma skin cancer has been found based on epidemiological data. There is evidence that one study included a population consisting of 71,533 cases of basal cell carcinoma and 8,629 cases of squamous cell carcinoma, in a control group of 1,430,833 and 172,462 cases, respectively. The use of high doses of hydrochlorothiazide (total dose ≥50,000 mg) was characterized by the following adjusted odds ratios of 1.29 (95% CI: 1.23-1.35) for basal cell carcinoma and 3.98 (95% CI: 3.68-4.31) for squamous cell carcinoma. A pronounced cumulative dose-response relationship was observed for basal cell carcinoma and squamous cell carcinoma. Another study showed a possible association between lip cancer (squamous cell carcinoma) and hydrochlorothiazide exposure: 633 cases of lip cancer were found in the 63,067 controls (using a risk-adjusted sampling strategy). The cumulative dose-response relationship was demonstrated by an adjusted odds ratio of 2.1 (95% CI: 1.7-2.6). This increased to 3.9 (3.0-4.9) for high doses of hydrochlorothiazide (25,000 mg) and to 7.7 (5.7-10.5) for the highest cumulative doses (100,000 mg).
Pharmacokinetics.
Valsartan.
After oral administration, valsartan and hydrochlorothiazide are rapidly absorbed, but the extent of absorption varies widely. The average absolute bioavailability of Diocor is 23%. The pharmacokinetic curve of valsartan has a descending multiexponential nature (T1/2α < 1 hour and T1/2β almost 9 hours). In the range of doses studied, the kinetics of valsartan are linear. With repeated use of the drug, no changes in kinetic parameters were noted. When taking the drug once a day, cumulation is insignificant. The drug concentrations in blood plasma in women and men were the same. Valsartan is largely (94-97%) bound to serum proteins, mainly albumin. The equilibrium volume of distribution is low (about 17 l). Compared with hepatic blood flow (approximately 30 l/h), plasma clearance of valsartan is relatively slow (approximately 2 l/h). The excretion of valsartan with feces is 70% (of the amount of the oral dose). About 30% is excreted in the urine, mainly unchanged.
When valsartan is administered with food, the area under the concentration-time curve (AUC) is reduced by 48%, although from approximately 8 hours after dosing, plasma concentrations are similar in both the fasted and fed states. The reduction in AUC is not associated with a significant reduction in therapeutic effect.
Hydrochlorothiazide.
After oral administration, hydrochlorothiazide is absorbed very rapidly (tmax approximately 2 hours). The pharmacokinetics of the drug in the distribution and elimination phases are generally described by a biexponential descending curve; the terminal phase half-life is 6-15 hours. In the therapeutic dose range, the average AUC value increases in direct proportion to the increase in dose. With repeated administration, the pharmacokinetics of hydrochlorothiazide do not change; when administered once a day, cumulation is insignificant. When administered orally, the absolute bioavailability of hydrochlorothiazide is 60-80%. Excreted in the urine: more than 95% of the dose in unchanged form and approximately 4% in the form of 2-amino-4-chloro-m-benzenedisulfonamide hydrolysate.
When hydrochlorothiazide is administered with food, both an increase and a decrease in its systemic bioavailability have been observed compared with the corresponding figure when taken on an empty stomach. The range of these changes is small and clinically insignificant.
Valsartan/hydrochlorothiazide.
When taken simultaneously with valsartan, the systemic bioavailability of hydrochlorothiazide is reduced by approximately 30%. The simultaneous use of hydrochlorothiazide does not significantly affect the kinetics of valsartan. This interaction does not affect the effectiveness of the combined use of valsartan and hydrochlorothiazide. In controlled clinical studies, a clear antihypertensive effect of this combination was found, which exceeded the effect of each of the components separately, as well as the effect of placebo.
Pharmacokinetics in certain patient groups.
Elderly patients.
It is known that in some elderly patients the systemic exposure to valsartan was somewhat more pronounced than in young patients, but it was not clinically significant.
Available data suggest that in elderly patients, both healthy and those suffering from arterial hypertension, the systemic clearance of hydrochlorothiazide is lower than in healthy young volunteers.
Patients with renal impairment.
No dose adjustment is required for patients with creatinine clearance 30-70 ml/min.
There are no data on the use of the combination of valsartan/hydrochlorothiazide in patients with severe renal impairment (creatinine clearance < 30 ml/min) and patients on hemodialysis.
Renal excretion of hydrochlorothiazide occurs by passive filtration and active secretion into the renal tubular lumen. The state of renal function plays a major role in the pharmacokinetics of hydrochlorothiazide, given that this drug is excreted exclusively by the kidneys.
Liver dysfunction.
It is known that the systemic exposure of valsartan in patients with mild (n=6) and moderate (n=5) hepatic impairment was 2-fold higher than in healthy volunteers. There are no data on the use of valsartan in patients with severe hepatic impairment. Liver disease does not significantly affect the pharmacokinetics of hydrochlorothiazide, and therefore no dose reduction is required.
Indication
Essential hypertension in patients whose blood pressure is not adequately controlled by monotherapy.
Contraindication
Hypersensitivity to any of the components of the drug and to other sulfonamide-derived drugs.
Severe liver dysfunction, cirrhosis and cholestasis.
Severe renal impairment (creatinine clearance < 30 ml/min), anuria.
Refractory hypokalemia, hyponatremia, hypercalcemia, symptomatic hyperuricemia.
Pregnant women and women planning to become pregnant (see section “Use during pregnancy or breastfeeding”).
Concomitant use of angiotensin receptor antagonists (ARBs), including valsartan, or angiotensin-converting enzyme (ACE) inhibitors with aliskiren in patients with diabetes mellitus or renal impairment (glomerular filtration rate (GFR) < 60 mL/min/1.73 m2).
Interaction with other medicinal products and other types of interactions
Interactions associated with the combination of valsartan/hydrochlorothiazide.
Simultaneous use is not recommended.
Lithium. Reversible increases in serum lithium concentrations and toxicity have been reported when lithium preparations have been administered concomitantly with angiotensin-converting enzyme (ACE) inhibitors or thiazide diuretics, including hydrochlorothiazide. There is no experience with the concomitant use of valsartan and lithium preparations, and this combination is therefore not recommended. If use of the drug is necessary, it is recommended to monitor serum lithium concentrations during concomitant use.
Concomitant use requiring special caution.
Other antihypertensive agents. The antihypertensive effect of other antihypertensive agents may be enhanced when used concomitantly with Diocor (e.g. guanethidine, methyldopa, vasodilators, ACE inhibitors, angiotensin receptor antagonists, beta-blockers, calcium channel blockers and dopamine reuptake inhibitors).
Pressor amines (e.g., noradrenaline, adrenaline): A decreased response to pressor amines may be noted, but not to the extent that their use should be excluded.
Non-steroidal anti-inflammatory drugs (NSAIDs), including selective COX-2 inhibitors, acetylsalicylic acid >3 g/day and non-selective NSAIDs. The antihypertensive effect of both the angiotensin II antagonist and the thiazide component may be reduced when used concomitantly with non-steroidal anti-inflammatory drugs. Concomitant use of these medicinal products may lead to deterioration of renal function and an increase in serum potassium. Therefore, monitoring of renal function at the start of treatment and monitoring of adequate hydration of the patient are recommended.
Interactions associated with valsartan.
Dual blockade of the renin-angiotensin-aldosterone system (RAAS) with ARBs, ACE inhibitors or aliskiren. Caution should be exercised when ARBs, including valsartan, are used concomitantly with other RAAS-blocking agents such as ACE inhibitors or aliskiren, as the incidence of hypotension, syncope, hyperkalaemia and renal dysfunction (including acute renal failure) has been increased compared with monotherapy. Dual blockade of the renin-angiotensin-aldosterone system (RAAS) with ACE inhibitors, ARBs or aliskiren is not recommended. If dual blockade of the renin-angiotensin-aldosterone system is considered absolutely necessary, it should only be used under specialist supervision and with close monitoring of renal function, electrolytes and blood pressure.
The concomitant use of angiotensin receptor antagonists, including valsartan, or angiotensin-converting enzyme inhibitors with aliskiren is contraindicated in patients with type 1 and type 2 diabetes mellitus, diabetic nephropathy, or patients with severe renal impairment (glomerular filtration rate (GFR) < 60 mL/min/1.73 m2).
Simultaneous use is not recommended.
Transporters. In vitro studies have shown that valsartan is a substrate for the hepatic uptake transporter OATP1B1/OATP1B3 and the hepatic efflux transporter MRP2. The clinical significance of these findings is unknown. Concomitant use of inhibitors of the uptake transporter (e.g. rifampicin, cyclosporine) or efflux transporter (e.g. ritonavir) may increase systemic exposure to valsartan. Appropriate precautions should be taken when initiating or discontinuing concomitant use of these medicinal products.
No interactions. No clinically significant interactions have been observed with valsartan monotherapy when used with the following medicinal products: cimetidine, warfarin, furosemide, digoxin, atenolol, indomethacin, hydrochlorothiazide, amlodipine, glibenclamide. Digoxin and indomethacin may interact with hydrochlorothiazide in the valsartan/hydrochlorothiazide combination (see Interactions related to hydrochlorothiazide).
Interactions associated with hydrochlorothiazide.
Concomitant use requiring special caution.
Medicinal products associated with potassium loss and hypokalaemia. The risk of hypokalaemia is increased by concomitant use of saluretics, laxatives, corticosteroids, ACTH, amphotericin, carbenoxolone, penicillin G and salicylic acid derivatives. These medicinal products may potentiate the effect of hydrochlorothiazide on blood potassium levels, therefore blood potassium levels should be monitored.
Medicinal products that may induce torsades de pointes. Due to the risk of hypokalaemia, hydrochlorothiazide should be used with caution in combination with medicinal products that may induce torsades de pointes, in particular class Ia and III antiarrhythmics and some antipsychotics.
Drugs affecting serum sodium levels. The hyponatremic effect of diuretics may be enhanced by concomitant administration of drugs such as antidepressants, antipsychotics, antiepileptic drugs, etc. Caution is advised with prolonged use of these drugs.
Medications that can cause 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, intravenous erythromycin, halofantrine, ketanserin, mizolastine, pentamidine, sparfloxacin, terfenadine, intravenous vincamine).
Due to the risk of hypokalemia, hydrochlorothiazide should be used with caution with drugs that can cause torsades de pointes.
Digitalis glycosides: Thiazide diuretics may cause adverse effects such as hypokalemia or hypomagnesemia, which in turn increase the risk of cardiac arrhythmias in digitalis intoxication.
Calcium salts and vitamin D. With the simultaneous use of thiazide diuretics with vitamin D or calcium salts, potentiation of the increase in serum calcium levels is possible.
Concomitant use of thiazide diuretics with calcium salts may cause hypercalcemia in patients predisposed to hypercalcemia (e.g. patients with hyperparathyroidism, malignancy or vitamin D-mediated conditions) due to increased tubular calcium reabsorption.
Antidiabetic agents (oral agents, insulin). Thiazide diuretics may cause changes in glucose tolerance. It may be necessary to adjust the dose of insulin or oral hypoglycemic agents in patients with diabetes mellitus. Concomitant use of metformin and hydrochlorothiazide in renal insufficiency may lead to the development of lactic acidosis.
Beta-blockers and diazoxide: Concomitant use of thiazide diuretics, including hydrochlorothiazide, with beta-blockers may increase the risk of hyperglycemia. Thiazide diuretics, including hydrochlorothiazide, may enhance the hyperglycemic effect of diazoxide.
Medicines used to treat gout (probenecid, sulfinpyrazone and allopurinol). The dose of uricosuric agents that stimulate the excretion of uric acid may need to be adjusted, as hydrochlorothiazide may increase serum uric acid levels. An increase in the dose of probenecid or sulfinpyrazone may be necessary. Concomitant use of thiazide diuretics, including hydrochlorothiazide, may increase the frequency of hypersensitivity reactions to allopurinol.
Amantadine: Thiazides, including hydrochlorothiazide, may increase the risk of side effects of amantadine.
Ion exchange resins. The absorption of thiazide diuretics, including hydrochlorothiazide, is reduced by cholestyramine or colestipol. This may result in subtherapeutic effects of thiazide diuretics. However, staggering the timing of hydrochlorothiazide and the resin so that hydrochlorothiazide is taken at least 4 hours before or 4 to 6 hours after the resin may minimize the risk of interaction.
Cytotoxic agents (e.g. cyclophosphamide, methotrexate): Thiazides, including hydrochlorothiazide, may reduce the renal excretion of cytotoxic agents and enhance their myelosuppressive effects.
Non-depolarizing muscle relaxants (e.g. tubocurarine). Thiazides, including hydrochlorothiazide, potentiate the effects of curare-like muscle relaxants.
Cyclosporine: Concomitant use of cyclosporine may increase the risk of hyperuricemia and symptoms resembling gout flares.
Alcohol, anesthetics and sedatives: When thiazide diuretics are used concomitantly with drugs that can also lower blood pressure (e.g. by reducing the activity of the sympathetic central nervous system or by direct vasodilator action), potentiation of orthostatic hypotension is possible.
Methyldopa: Cases of hemolytic anemia have been reported with the concomitant use of hydrochlorothiazide and methyldopa.
Carbamazepine: The risk of hyponatremia may be increased. Such patients should be informed of the possibility of a hyponatremic reaction and should be monitored clinically and with blood laboratory tests.
Contrast media containing iodine. Dehydration caused by diuretics may increase the risk of acute renal failure, especially with high doses of iodine-containing contrast media. Fluid balance should be restored before iodine administration.
Application features
Changes in electrolyte balance. Caution should be exercised when using Diocor with potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes, and drugs that may increase blood potassium levels (e.g. heparin). Cases of hypokalemia have been reported during treatment with thiazide diuretics. Regular monitoring of serum potassium is recommended. Thiazide diuretic therapy is frequently associated with hyponatremia and hypochloremic alkalosis. Thiazides increase urinary magnesium excretion, which may result in hypomagnesemia. As in any patient receiving diuretic therapy, serum electrolyte levels should be determined periodically at appropriate intervals.
Patients with sodium and/or volume depletion. In patients with severe sodium and/or volume depletion, such as those receiving high doses of diuretics, symptomatic hypotension may occasionally occur at the beginning of treatment with the drug. Therefore, correction of sodium and/or volume depletion is recommended before starting treatment with Diocor. In the event of hypotension, the patient should be placed in the horizontal position and, if necessary, an intravenous infusion of saline should be given. After stabilization of blood pressure, treatment can be continued.
Patients with severe heart failure or other cases of activation of the renin-angiotensin-aldosterone system. In patients whose renal function depends on the activity of the renin-angiotensin-aldosterone system (e.g. patients with severe congestive heart failure), treatment with ACE inhibitors may cause oliguria and/or progressive azotemia, in some cases - lead to the development of acute renal failure. The use of the drug in patients with severe chronic heart failure is not justified, since it cannot be excluded that due to inhibition of the renin-angiotensin-aldosterone system, the use of valsartan may also be associated with impaired renal function, the drug Diocor should not be used in such patients.
Renal artery stenosis: In patients with unilateral or bilateral renal artery stenosis or stenosis of the artery to a solitary kidney, valsartan may increase plasma creatinine or blood urea and should not be used in these patients.
Primary hyperaldosteronism: The drug should not be used in patients with primary hyperaldosteronism, as their renin-angiotensin-aldosterone system is not activated.
Renal impairment. When using the drug in patients with mild or moderate renal impairment (creatinine clearance > 30 ml/min), dose adjustment is not required, but periodic monitoring of serum potassium, creatinine and uric acid is recommended. It should be used with caution in severe renal failure (creatinine clearance < 30 ml/min). Thiazide diuretics can provoke azotemia in patients with chronic renal failure. They are ineffective as monotherapy in severe renal failure (creatinine clearance < 30 ml/min), but they can be used with due caution in combination with loop diuretics even in patients with creatinine clearance < 30 ml/min. The concomitant use of angiotensin receptor antagonists, including valsartan, or angiotensin-converting enzyme inhibitors with aliskiren is contraindicated in patients with renal impairment (glomerular filtration rate (GFR) < 60 mL/min/1.73 m2).
Kidney transplantation: There are no data on the safety of valsartan in patients with a recent kidney transplantation.
Hepatic impairment. No dose adjustment is required in patients with mild to moderate hepatic impairment without cholestasis. However, the drug should be used with caution. Liver disease does not significantly alter the pharmacokinetics of hydrochlorothiazide.
Systemic lupus erythematosus: Thiazide diuretics have been reported to cause exacerbation or activation of systemic lupus erythematosus.
Other metabolic disorders: Thiazide diuretics may cause changes in glucose tolerance and increases in serum cholesterol, triglycerides and uric acid.
Diabetic patients may require adjustment of insulin or oral hypoglycemic agents. Thiazides may reduce urinary calcium excretion and cause intermittent and minor increases in serum calcium in the absence of known disorders of calcium metabolism. Significant hypercalcemia may indicate latent hyperparathyroidism. Thiazides should be discontinued prior to parathyroid function testing.
Photosensitivity: There have been reports of photosensitivity with the use of thiazide diuretics.
If a photosensitivity reaction occurs during treatment, treatment with the drug should be discontinued. If it is necessary to re-administer the diuretic, it is recommended to protect the affected areas from sunlight or artificial ultraviolet radiation.
Non-melanoma skin cancer: Two epidemiological studies based on data from the Danish National Cancer Registry have shown an increased risk of non-melanoma skin cancer (NSCLC) (basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)) following the use of higher total doses of hydrochlorothiazide.
The photosensitizing effect of hydrochlorothiazide may be a possible mechanism for the development of NMSD. Patients taking hydrochlorothiazide should be informed of the risk of NMSD, the need to regularly inspect the skin for new lesions and to immediately report any suspicious skin lesions. To reduce the risk of developing skin cancer, patients should be informed of possible preventive measures, such as limiting exposure to sunlight and UV rays, and in case of exposure, adequate skin protection should be provided. Suspicious skin lesions should be examined as soon as possible, including histological examination of biopsy material. Patients with a history of NMSD may also need to reconsider the use of hydrochlorothiazide.
Pregnancy. Angiotensin II receptor antagonists should not be initiated during pregnancy. Unless continued angiotensin II receptor antagonist 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 angiotensin II receptor antagonists should be stopped immediately, and, if appropriate, alternative therapy should be started.
General: Special caution should be exercised when administering the drug to patients who have shown hypersensitivity to other angiotensin II receptor antagonists. Allergic reactions to hydrochlorothiazide are more likely to occur in patients with allergies and asthma.
Angioedema. Angioedema (including swelling of the larynx and glottis leading to airway obstruction and/or swelling of the face, lips, pharynx and/or tongue) has been reported in patients treated with valsartan, some of whom had a history of angioedema with other drugs, including other angiotensin II receptor antagonists. If angioedema develops, treatment with the drug should be discontinued immediately. Re-administration is contraindicated.
Drugs containing sulfonamide or sulfonamide derivatives may cause an idiosyncratic reaction resulting in choroidal effusion with visual field defect, transient myopia, and acute angle-closure glaucoma. Symptoms include acute onset of decreased visual acuity or eye pain and usually occur within hours to weeks of starting the drug.
Untreated acute angle-closure glaucoma can lead to permanent vision loss. The main treatment is to stop the medication as soon as possible. If the intraocular pressure remains uncontrolled, urgent medical or surgical treatments may be necessary. Risk factors for developing acute angle-closure glaucoma may include a history of sulfonamide or penicillin allergy.
Acute respiratory toxicity. Very rare cases of severe acute respiratory toxicity (ART), including acute respiratory distress syndrome (ARDS), have been reported with hydrochlorothiazide. Initial symptoms of ART include dyspnea, fever, worsening of pulmonary function, and hypotension. Pulmonary edema usually develops within minutes to hours of taking hydrochlorothiazide. If ARDS is suspected, hydrochlorothiazide should be discontinued and appropriate treatment initiated. The drug should not be prescribed to patients who have previously experienced ARDS after taking hydrochlorothiazide.
No dose adjustment is required for elderly patients.
Hydrochlorothiazide may reduce the level of protein-bound iodine in the blood plasma.
Hydrochlorothiazide is capable of increasing the concentration of free bilirubin in the blood serum.
Use during pregnancy or breastfeeding
Pregnancy.
Valsartan.
The use of angiotensin II receptor antagonists is contraindicated in pregnant women and women planning to become pregnant.
If pregnancy is detected during treatment with Diocor, it should be immediately discontinued and, if necessary, replaced with another drug approved for use in pregnant women.
Women planning pregnancy should be given alternative antihypertensive treatments with an established safety profile for use in pregnancy.
It is known that the use of angiotensin II receptor antagonists during the second and third trimesters may induce fetotoxicity (decreased renal function, oligohydramnios, delayed skull ossification) and neonatal toxicity (renal failure, hypotension, hyperkalemia).
Should exposure to angiotensin II receptor antagonists have occurred from the second trimester of pregnancy, ultrasound check of renal function and skull is recommended.
Infants whose mothers have taken angiotensin II receptor antagonists should be closely observed for hypotension.
Hydrochlorothiazide.
Given the mechanism of action of angiotensin II receptor antagonists, a risk to the fetus cannot be excluded when Diocor is used during the first trimester of pregnancy. Animal studies are known to be insufficient.
Hydrochlorothiazide crosses the placenta. Based on the pharmacological mechanisms of action of hydrochlorothiazide, its use during the 2nd and 3rd trimesters of pregnancy may lead to impaired fetoplacental circulation and cause effects in the fetus and newborn such as jaundice, electrolyte imbalance and thrombocytopenia.
Breastfeeding period.
If the use of the drug is absolutely necessary, breastfeeding should be discontinued. There is no information on the use of valsartan during breastfeeding. Hydrochlorothiazide passes into breast milk in small amounts. Thiazides in high doses cause diuresis, which may lead to a decrease in breast milk production. During breastfeeding, alternative treatments with better established safety profiles during nursing a newborn or preterm infant are preferable.
Ability to influence reaction speed when driving vehicles or other mechanisms
At the beginning of drug therapy (the period is determined individually by the doctor) it is forbidden to drive a car and perform work that may lead to an accident. Later, the degree of prohibition is determined by the doctor.
