Firma ND 300 - instructions for use, dose, side effects, contraindications

* Foam 85F34353 II pink: polyvinyl alcohol 9.60 mg, titanium dioxide (E171) 5.90 mg, macrogol 4.85 mg, talc 3.55 mg, iron dye oxide yellow (E172) 0.060 mg, iron dye oxide red (E172) 0.038 mg

Description:

The capsule-shaped form is biconvex tablets coated with a filmy coating of light pink color.

View of the fracture: a rough mass of white or almost white with a filmy coating of light pink color.

Pharmacotherapeutic group:hypotensive combined agent (angiotensin II receptor antagonist [ARA II] + diuretic).

ATX: & nbsp

C.09.D.A.04 Irbesartan in combination with diuretics

C.09.D.A Angiotensin II antagonists in combination with diuretics

Pharmacodynamics:

The drug Firmast® ND 300 is a combination of ARA II - irbesartan and thiazide diuretic hydrochlorothiazide. The combination of these ingredients has an additive antihypertensive effect, reducing blood pressure (BP) more than each of them individually.

Irbesartan is a selective ARA II (of the type AT |). Irbesartan does not require metabolic activation to acquire pharmacological activity. Angiotensin II is an important component of the renin-angiotensin-aldosterone system (RAAS) and is involved in the pathogenesis of the development of arterial hypertension (AH), as well as the homeostasis of sodium. Irbesartan blocks all physiologically significant effects of angiotensin II, irrespective of the source or route of its synthesis, including its pronounced vasoconstrictive and aldosterone-secreting effects realized through AT receptors located on the surface of the smooth muscle cells of the vessels and in the adrenal cortex. Irbesartan does not have agonistic activity with respect to AT₁ receptors and has a much greater (more than 8500 times) affinity for AT₁receptors than to AT₂-receptors (receptors, not associated with regulation of the cardiovascular system).

Irbesartan does not inhibit RAAS enzymes (such as renin, angiotensin-converting enzyme [AIF]) and does not affect the receptors of other hormones or ion channels involved in the regulation of blood pressure and sodium homeostasis. Blocking irbesartan AT | - receptors interrupts the feedback loop in the renin-angiotensin system, which leads to an increase in the concentration of renin and angiotensin II in the blood plasma. After taking irbesartan in recommended doses, the plasma concentration of aldosterone decreases, without significantly affecting the potassium content in the blood serum (the mean value of its increase is <0.1 mEq / L). Irbesartan has no significant effect on serum concentrations of triglycerides, cholesterol and glucose. Irbesartan does not affect the concentration of uric acid in the blood serum or the rate of excretion of uric acid by the kidneys.

Hydrochlorothiazide is a thiazide diuretic with diuretic, natriuretic and antihypertensive action. The mechanism of antihypertensive the action of thiazide diuretics, for example, hydrochlorothiazide, is not completely known. Thiazide diuretics affect tubular mechanisms of reabsorption of electrolytes in the kidneys, approximately equally increasing the excretion of sodium and chloride ions. Sodium sulfur leads to a secondary loss of potassium and bicarbonate ions. Hydrochlorothiazide increases the plasma renin activity (ARP) and aldosterone secretion, and also reduces the potassium content in the blood serum. Simultaneous administration of ARA II helps reduce the loss of potassium ions associated with the action of thiazide diuretics. The antihypertensive effect of irbesartan in combination with hydrochlorothiazide manifests itself after taking its first dose and becomes significant within 1-2 weeks of admission, its maximum antihypertensive effect is achieved by 6-8 weeks of treatment.In long-term clinical trials, the antihypertensive effect of the combination irbesartan / hydrochlorothiazide was observed for more than one year.

The combination of irbesartan / hydrochlorothiazide when administered in the therapeutic dose range has a dose-dependent and additive antihypertensive effect. The blood pressure is reduced to the same extent in the "standing" and "lying" positions. Orthostatic effects are rare, but their occurrence is possible in patients with hyponatraemia and / or hypovolemia.

The efficacy of irbesartan / hydrochlorothiazide combination does not depend on age, race or gender. The overall antihypertensive response to a combination in patients of the Negroid race and patients of other races was similar.

After discontinuing irbesartan, blood pressure gradually returns to the initial values. The syndrome of "withdrawal" in irbesartan and hydrochlorothiazide is not observed. When hydrochlorothiazide is taken inside, the diuretic effect occurs within the first 2 hours, the diuresis reached a maximum in about 4 hours and lasted about 6-12 hours. A significant advantage of the antihypertensive effect of the combination irbesartan / hydrochlorothiazide (in dosesfrom 12.5 / 150 mg to 25/300 mg) as initial therapy in patients with moderate to severe AH, compared with initial irbesartan monotherapy (doses 150 mg to 300 mg) and hydrochlorothiazide ( in doses from 12.5 mg to 25 mg).

Pharmacokinetics:

Neither irbesartan, nor hydrochlorothiazide Do not change the pharmacokinetics of each other.

Suction

Irbesartan and hydrochlorothiazide are active substances when taken orally and do not need biotransformation for their transformation into an active form.

After ingestion of Finasta® ND 300, the absolute bioavailability of irbesartan is 60-80%, and hydrochlorothiazide is 50-80%. Eating does not affect the bioavailability of the active substances of the drug. After taking the drug Firmast ® ND 300 inside the maximum concentrations in the blood serum (C_m_Oh) are achieved after 1.5-2 hours for irbesartan and after 1-2.5 hours for hydrochlorothiazide.

Distribution

The connection of irbesartan with plasma proteins is approximately 96%, its association with the cellular components of the blood is insignificant. The volume of irbesartan distribution is 53-93 l (0.72-1.24 l / kg).The ratio of hydrochlorothiazide to plasma proteins is 68%, and its volume of distribution is 3.6-7.8 l / kg.

Metabolism

After ingestion or intravenous administration ¹⁴C-irbesartan 80-85% of the radioactivity circulating in the blood plasma is due to the unchanged irbesartan. Irbesartan metabolized by the liver by oxidation and conjugation with glucuronic acid. The main metabolite in the systemic circulation is irbesartan glucuronide (approximately 6%). Oxidation of irbesartan is carried out, mainly, with the help of the isoenzyme of the cytochrome P450 system CYP2C9, isoenzymatic participation CYP3A4 in the metabolism of irbesartan is insignificant. Irbesartan It is not metabolized by most isoenzymes, which are usually involved in the metabolism of drugs (isoenzymes CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2D6 or CYP2E1), and does not cause their inhibition or induction. Irbesartan Does not induce or inhibit isoenzyme CYP3A4. Excretion

Irbesartan and its metabolites are excreted from the body, both through the intestines (with bile) and the kidneys. After ingestion or intravenous administration ¹⁴C-irbesartan 20% of radioactivity is found in the urine, and the rest - in the feces.Less than 2% of the administered dose is excreted by the kidneys in the form of unchanged irbesartan. Hydrochlorothiazide It is not metabolized and excreted by the kidneys. Mean values of plasma half-life (T_1/2) hydrochlorothiazide is 5-15 hours. Hydrochlorothiazide penetrates the placental barrier and is excreted into breast milk. The final T_1/2 is 11-15 hours. The total clearance of intravenously administered irbesartan is 157-176 ml / min, and its renal clearance is 3-3.5 ml / min. With a daily once-daily irbesartan intake, the equilibrium plasma concentration (Css) is reached after 3 days, while its limited accumulation in blood plasma (less than 20%) is observed.

Pharmacokinetics in selected patient groups

Influence of sex on the pharmacokinetics of irbesartan

In women (but compared with men), slightly higher plasma concentrations of irbesartan are noted. However, the differences associated with the ion in T_1/2 and the accumulation of irbesartan is not detected. Correction of irbesartan dose in women is not required. There were no gender-related differences in the effects of irbesartan.

The pharmacokinetics of irbesartan in elderly patients

The values of area "concentration-time" (AUC) and C_m_Oh in blood plasma irbesartan in elderly patients (65-80 years old) with clinically normal renal and hepatic function were approximately 20-50% higher than in patients of younger age (18-40 years). Finite T_1/2 they were comparable. There were no age-related differences in the effects of irbesartan.

The pharmacokinetics of irbesartan in patients with impaired hepatic function

In patients with mild (functional class A or 5-6 points on the Child-Pugh scale) and moderately expressed (functional class 13 or 7-9 on the Child-Pugh scale), hepatic insufficiency due to cirrhosis of the liver does not significantly alter the pharmacokinetic parameters of irbesartan.

The pharmacokinetics of irbesartan in patients with impaired renal function

In patients with impaired renal function or patients undergoing hemodialysis, the pharmacokinetics of irbesartan do not change significantly. Irbesartan is not excreted from the body by hemodialysis.

Influence of race on the pharmacokinetics of irbesartan

In volunteers without AH AUC and T_1/2 irbesartan in patients or representatives of the Negroid race were approximately 20-25% higher than in patients or representatives of the Caucasoid race, C_m_Oh irbesartan in blood plasma they were almost the same.

Indications:Arterial hypertension of moderate or severe severity (treatment of patients who are shown combined antihypertensive therapy).

Contraindications:

- Hypersensitivity to the active substances of the drug, to any of the excipients of the drug Firmas® ND 300 (see the "Composition" section) or to other derivatives of sulfonamide (hydrochlorothiazide is a sulfonamide derivative).

- Simultaneous use with medicinal products containing aliskiren, in patients with diabetes mellitus or with moderate and severe renal failure (glomerular filtration rate [GFR] <60 mL / min / 1.73 m² surface area of the body).

- Simultaneous use with ACE inhibitors in patients with diabetic nephropathy.

- Severe renal failure (creatinine clearance (CK) is less than or equal to 30 ml / min), anuria (due to the presence of hydrochlorothiazide in the formulation).

- Pregnancy.

- Breastfeeding period.

- Age to 18 years (effectiveness and safety not established).

Carefully:

- In patients with stenosis of the aortic or mitral valve or hypertrophic obstructive cardiomyopathy (GOKMP).

- In patients with hypovolemia, hyponatremia, for example, with intensive diuretic therapy, hemodialysis, adherence to a diet with restricted intake of table salt, diarrhea, vomiting (danger of excessive blood pressure lowering, see "Special instructions").

- In patients with renal function dependent on RAAS activity, such as patients with AH with bilateral or unilateral renal artery stenosis or patients with chronic heart failure (CHF) III-IV functional class (according to the NYHA classification) (see section "Special instructions" ),

- In patients with coronary heart disease (CHD) and / or atherosclerotic lesions of cerebral vessels (the risk of increased myocardial or brain ischemia, up to the development of myocardial infarction [MI] or stroke with excessive lowering of blood pressure).

- In patients with mild and moderate renal insufficiency (QC from 60 to 30 ml / min) (risk of increased azotemia, increased concentration of uric acid in the blood serum [due to the presence of hydrochlorothiazide in the formulation] and the development of hyperkalemia [due to the presence in the composition of irbesartan]).

- In patients after kidney transplantation (lack of clinical experience).

- In patients with hepatic insufficiency of all degrees of severity or with progressive liver diseases (due to the presence of hydrochlorothiazide in the formulation, since even minor violations of the water-electrolyte balance in such patients can provoke a hepatic coma).

- In patients with diabetes mellitus (due to the presence of hydrochlorothiazide in the formulation, it is possible to reduce glucose tolerance, increase the need for insulin and hypoglycemic agents for oral administration).

- In patients with gout (in connection with the presence of hydrochlorothiazide in the drug may increase the concentration of salts of uric acid in the blood serum).

- In patients with hyperkalemia, while taking potassium-sparing drugs and / or potassium-containing salt substitutes (risk of hyperkalemia).

- In patients with systemic lupus erythematosus (due to the presence of hydrochlorothiazide in the formulation, since there are reports of exacerbation or weight gain of systemic lupus erythematosus with the use of thiazide diuretics).

- With the simultaneous administration of other antihypertensive drugs (the possibility of potentiating their antihypertensive effect).

- In patients with sympathectomy (the risk of increasing the antihypertensive effect of hydrochlorothiazide).

- When used in combination with ACE inhibitors or aliskiren, as compared with irbesartan alone, with double blockade of RAAS, there is an increased risk of developing excessive blood pressure lowering, hyperkalemia and changes in kidney function (see section "Special instructions").

- In patients with allergic reactions to penicillins and sulfanilamides in history, which are risk factors for the development of an idiosyncratic reaction - acute closed-angle glaucoma with the use of sulfonamides or sulfonamide derivatives (see section "Special instructions", subsection "Acute myopia and secondary acute angle-closure glaucoma").

Pregnancy and lactation:

Pregnancy

Experience with the use of the combination irbesartan / hydrochlorothiazide in pregnancy is absent.

Taking into account the fact that during the reception of ACE inhibitors by pregnant women in the second and third trimesters of pregnancy, the developing fetus was damaged and died,the use of the drug Firmast® ND 300 during pregnancy, as well as any other drug directly affecting RAAS, is contraindicated.

Thiazide diuretics penetrate the placental barrier and are found in the umbilical cord blood. The use of diuretics in pregnant women is not recommended, as fetal or neonatal jaundice, thrombocytopenia and other unwanted reactions that occur in adults are possible.

When diagnosing pregnancy during treatment with the drug Firmast® ND 300, it should be stopped as soon as possible.

Breastfeeding period

It is not known whether the irbesartan or its metabolites into breast milk, hydrochlorothiazide penetrates into breast milk. Thiazide diuretics when used in high doses, causing intense diuresis, can suppress lactation. The drug Firmast® ND 300 is contraindicated for use throughout the whole period of breastfeeding because of the potential risk to the infant. Therefore, after evaluating the ratio of the perceived benefit from taking the drug to the mother and the potential risk to the baby, stop breastfeeding, or take the drug Firmast® ND 300.

Dosing and Administration:

The drug Firmast® ND 300 is taken once a day, regardless of the time of food intake.

The drug Firmast® ND 300 should be used in patients whose blood pressure is not adequately controlled by irbesartan or hydrochlorothiazide in monotherapy. The drug Firmast® ND 300 (tablets containing hydrochlorothiazide 25 mg and irbesartan 300 mg) can be used in patients in whom BP is not adequately controlled by the preparation of Firmas® H 300.

When used in patients in whom BP is not adequately controlled by the preparation of Firmast® ND 300, the doses of the active substances in combination can be increased to 300 mg of irbesartan and 25 mg of hydrochlorothiazide per day: 2 tablets of Finamast® ND 150 (tablets containing hydrochlorothiazide 12.5 mg and irbesartan 150 mg) or one tablet of the drug Firmast® ND 300 (tablets containing hydrochlorothiazide 25 mg and irbesartan 300 mg).

The maximum daily dose: 1 tablet of the drug Firmas® ND 300 (tablets containing hydrochlorothiazide 25 mg and irbesartan 300 mg) (recalculation of the daily dose for irbesartan - 300 mg / day and hydrochlorothiazide - 25 mg / day).

If it is not possible to achieve the target values of blood pressure for therapy only with the drug Firmas ND 300,then to add it can receive treatment with other antihypertensive drugs (e.g., bsta-blockers and blockers "slow" calcium channel (BCCI) long-acting).

As initial therapy in patients who are supposed to be based on the severity of the disease, will need to conduct combination antihypertensive therapy, treatment is initiated with drug Firmasta® H 150 (Tablets containing hydrochlorothiazide 12.5 mg and irbesartan 150 mg), taken once a day. If necessary, a larger decrease in blood pressure dose may be increased after 1-2 weeks of treatment up to a maximum dose of 25 mg of hydrochlorothiazide and irbesartan 300mg once daily (possibly use Firmasta® LP 300 formulation).

Use in selected patient groups

Children and teens

To date, the safety and efficacy of the combination irbesartan / hydrochlorothiazide in children and adolescents has not been established.

Elderly patients

Usually, elderly patients do not need a dose reduction. In patients who took the irbesartan / hydrochlorothiazide combination in clinical studies, in general,There was no difference in efficacy and safety between patients 65 years of age and older and younger patients.

Patients with hepatic insufficiency

Usually in patients with impaired liver function (mild and moderate severity

- 5-6 and 7-9 on the Child-Pugh scale, respectively) no dose reduction is required. In view of the presence of hydrochlorothiazide in the formulation, special care should be taken when using the drug in patients with severe hepatic impairment (more than 9 on the Child-Pugh scale).

Patients with renal insufficiency

Usually in patients with renal insufficiency (mild to moderate severity

CK> 30 ml / min) dose reduction is not required. However, due to the presence of hydrochlorothiazide in patients with severe renal failure as part of the preparation of Firmast® ND 300 hydrochlorothiazide, the use of the drug Firmast® ND 300 is not recommended (QC < 30 ml / min) (see section "Special instructions").

Patients with hypovolaemia

- In patients with severe hypovolemia and / or hyponatremia, for example, in patients receiving intensive diuretic therapy, hypovolemia and hyponatremia should be corrected before the application of the drug Firmast® ND 300 (see section "Special instructions").

Side effects:

The following undesirable phenomena (AEs) are presented in accordance with the following grades of their incidence according to the classification of the World Health Organization: very often (> 1/10), often (> 1/100, <1/10), infrequently (> 1/1000, <1/100), rarely (> 1/10000, <1/1000), very rarely (<1/10000, including individual messages), unknown frequency (it is not possible to determine the incidence of AE from the available data).

In clinical AE studies, patients treated with irbesartan / hydrochlorothiazide for 6 months and one year or more were usually mild and transient, and their incidence was not related to the dose taken. The incidence of AEs also did not depend on the age, sex and race of the patients.

In placebo-controlled studies in patients receiving the combination

irbesartan / hydrochlorothiazide (the usual duration of treatment is 2-3 months),

discontinuation of treatment due to any clinical or laboratory AEs was

significantly less frequent in patients taking the combination

irbesartan / hydrochlorothiazide than in patients taking placebo.

BUT, observed with the combination of irbesartan / hydrochlorothiazide in

clinical trials in patients with AH

Impaired nervous system:

often: dizziness, headache;

infrequently: orthostatic dizziness.

Heart Disease:

infrequently: tachycardia, changes in the electrocardiogram.

Vascular disorders:

infrequently: excessive reduction of blood pressure, peripheral edema, in particular, edema of the lower extremities, "hot flashes" of blood to the skin of the face, syncopal conditions.

Disorders from the gastrointestinal tract:

often: nausea / vomiting;

infrequently: diarrhea, dryness of the oral mucosa, abdominal pain.

Disorders from the kidneys and urinary tract:

often: changes in frequency of urination.

Violations of the genitals and breast:

infrequently: sexual dysfunction (weakening of libido, erectile dysfunction).

General disorders and disorders at the site of administration:

often: increased fatigue;

infrequently: weakness.

Disturbances from the skin and subcutaneous tissues: infrequent: skin rash, itchy skin.

Disturbances from the musculoskeletal and connective tissue: infrequently: myalgia, bone pain, weakness in the extremities.

BUT, observed in placebo-controlled studies using irbesartan / hydrochlorothiazide combination as initial treatment in patients with severe and moderate AH

Initial treatment with irbesartan / hydrochlorothiazide

The combinations of irbesartan / hydrochlorothiazide, presented below, in clinical studies conducted in patients with AH of severe and moderate severity were similar to those described above, observed in previous clinical trials with AH.

In a clinical study with AH of moderate severity (mean diastolic blood pressure (DBP), in a sitting position of 90-110 mm Hg), the types and frequency of AE observed in patients treated with irbesartan / hydrochlorothiazide as a combination initial therapy were similar to the AE profile in patients who received initial treatment as monotherapy with irbesargan or hydrochlorothiazide. There were no cases of syncopal conditions in the combination therapy group, and in the monotherapy group with hydrochlorothiazide, one case of syncope was recorded.

The frequency of the above-mentioned AEs in combination with irbesartan / hydrochlorothiazide, monotherapy with irbesargan and hydrochlorothiazide monotherapy, respectively, was 0.9%, 0% and 0% for excessive reduction in blood pressure, 3.0%, 3.8%, and 1, 0% for dizziness, 5.5%, 3.8% and 4.8% for headache, 1.2%, 0% and 1.0% for hyperkalemia and 0.9%, 0% and 0 % - for hypokalemia.

The frequency of cancellation due to AEs in combination with irbesartan / hydrochlorothiazide, monotherapy with irbesartai and monotherapy with hydrochlorothiazide was 6.7%, 3.8% and 4.8%, respectively. In a clinical study conducted with severe AH (DBP in the "sitting" > 110 mm Hg. The overall picture of AE during 7 weeks of follow-up was similar in patients treated with irbesartan / hydrochlorothiazide as initial therapy, and in patients receiving initial therapy irbesartan. The frequency of the above AE for the combination irbesartan / hydrochlorothiazide and irbesartan was, respectively: 0% and 0% for the syncope, 0.6% and 0% for excessive blood pressure lowering, 3.6% and 4.0% for vertigo, 4.3% and 6.6% for headache, 0.2% and 0% for hyperkalemia and 0.6%, and 0.4% for hypokalemia, respectively.

The frequency of cancellation of treatment due to AEs when taking the combination irbesartan / hydrochlorothiazide and with monotherapy with irbesartan was 2.1% and 2.2%, respectively.

Laboratory and instrumental data

Clinically significant changes in the results of laboratory studies during controlled clinical trials of irbesartan / hydrochlorothiazide combination have not been revealed.

Experience of post-registration application

Irbesartan

As in the case of other ARA II, extremely rare cases of development of hypersensitivity reactions (angioedema, urticaria) were observed with monotherapy with irbesartan. In addition, with the post-marketing application of irbesartan, the following AEs were observed: vertigo, asthenia, hyperkalemia, jaundice, myalgia, increased functional hepatic test, hepatitis, ringing in the ears and impaired renal function, including cases of acute renal failure in patients at risk.

Hydrochlorothiazide

In monotherapy with hydrochlorothiazide, the following AEs were observed (regardless of their association with hydrochlorothiazide): anorexia, irritation of the gastric mucosa, diarrhea, constipation,jaundice (associated with intrahepatic cholestasis), pancreatitis, sialadenitis, vertigo, paresthesia, xantopsy, leukopenia, neutropenia / agranulocytosis, thrombocytopenia, aplastic anemia, hemolytic anemia, reactions photosensitization, fever, urticaria, necrotizing angiitis (vasculitis, cutaneous vasculitis), respiratory distress syndrome (including pneumonitis and pulmonary edema), anaphylactic reactions, toxic epidermal necrolysis, hyperglycemia, glucosuria, hyperuricemia, water-electrolyte balance disorders (including hyponatremia and hypokalemia ), renal dysfunction, interstitial nephritis, muscle spasms, weakness, anxiety, transient visual impairment.

Overdose:

Symptoms

The most common symptoms observed in adults with an overdose of hydrochlorothiazide were symptoms caused by water-electrolyte disturbances in blood composition (hypokalemia, hypochloraemia, hyponatremia) and dehydration resulting from excessive diuretic effect. In the case of simultaneous reception of cardiac glycosides (eg, digoxin) or antiarrhythmic agents (eg, sotalol), hypokalemia may contribute to the development of rhythm disturbances.Overdose of the drug Firmast® ND 300 may lead to an excessive decrease in blood pressure, the development of bradycardia and tachycardia.

There is an experience of taking irbesartan in doses up to 900 mg / day for 8 weeks without

development of toxic effects.

Treatment

There is no specific information on the treatment of an overdose of irbesartan / hydrochlorothiazide combination. Continuous monitoring of the patient's condition should be established and, if necessary, symptomatic and supportive therapy, including recovery of fluid and electrolyte losses. In case of overdose, it is recommended to induce vomiting and / or gastric lavage. Irbesartan is not excreted from the body by hemodialysis. The degree of excretion of hydrochlorothiazide by hemodialysis is not established.

Interaction:Based on in vitro studies, no interaction of irbesartan with drugs metabolized by isoenzymes CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2E1 or CYP3A4 is expected. Irbesartan, is mainly metabolized by the CYP2C9 isoenzyme and, to a lesser extent, is glucuronidated.No significant pharmacokinetic and pharmacodynamic interactions were observed with the simultaneous use of irbesartan with warfarin, a drug metabolized by isoenzyme CYP2C9. Irbesartan does not change the pharmacokinetics of digoxin and simvastatin. With the simultaneous use of irbesartan with hydrochlorothiazide or nifedipine, the pharmacokinetics of irbesartan does not change.

Medicinal preparations containing adipes

Combination of the drug Firmast® ND 300 with medicinal products containing aliskiren, is contraindicated in patients with diabetes mellitus or with moderate or severe renal failure (GFR <60 mL / min / 1.73 m² body surface area) and is not recommended in other patients (see the sections "Contraindications", "With caution", "Special instructions").

ACE Inhibitors

The use of the drug Firmast ® ND 300 simultaneously with ACE inhibitors is contraindicated in patients with diabetic nephropathy and is not recommended in other patients (see the sections "Contraindications", "With caution", "Special instructions").

Drugs affecting serum potassium levels

Based on the experience gained from the use of other drugs affecting the RAAS, while the use of potassium preparations salt substitute containing potassium, potassium-sparing diuretics or other, can raise the potassium content in the blood serum of drugs (e.g., heparin), may increase the content potassium in the blood serum. Necessary to monitor the content of potassium in the blood serum during therapy with Firmasta® ND 300. Simultaneously with the reception of hydrochlorothiazide irbesartan may reduce the incidence of this effect.

Nonsteroidal anti-inflammatory drugs (NSAIDs), including selective inhibitors of cyclooxygenase-2 (COX-2)

Elderly patients, patients with hypovolemia or patients with impaired renal function NSAIDs, including COX-2 inhibitors, simultaneously with ARA II, including irbesartan, can lead to impaired renal function, including the possible development of acute renal failure. These effects are usually reversible. Periodically monitor kidney function in patients who simultaneously take irbesartan and NSAIDs.With the simultaneous use of ARA II, including irbesartan, and NSAIDs, including selective inhibitors of COX-2, the attenuation of the antihypertensive effect of APA II is possible.

Ethanol, barbiturates or narcotic drugs

There may be an increase in orthostatic hypotension caused by thiazide diuretics.

Hypoglycemic agents for oral administration and insulin

As hydrochlorothiazide can increase the concentration of glucose in the blood, it may be necessary to increase the dose of hypoglycemic agent.

Antifungal Drugs

With the simultaneous use of the drug Firmast® ND 300 and antidotal drugs, correction of doses of antidotal drugs may be required, since hydrochlorothiazide may increase the serum concentrations of uric acid.

Cardiac glycosides, antiarrhythmics

With their simultaneous use with the drug Firmast ® ND 300 in the case of hypokalemia and hypomagnesemia caused by the thiazide diuretic entering into its structure, the risk of arrhythmias increases.

Salts of calcium

Thiazide diuretics can increase the serum calcium level.If the patient requires the use of calcium preparations or calcium-saving drugs (for example, vitamin D), it is necessary to monitor the calcium content in the blood serum and to carry out appropriate correction of the dosing regimen of calcium preparations.

Kolestyramine and colestipol

The absorption of hydrochlorothiazide in the presence of anion-exchange resins is reduced. It should be divided by the time of taking the drug Firmast® ND 300 and Colestipol or Colestyramine for at least 4 hours.

Lithium salts

Diuretics reduce renal clearance of lithium, in turn irbesartan increases serum lithium concentrations. All this increases the risk of developing toxic effects of lithium. Care should be taken when using the drug Firmast® ND 300 with lithium salts, it is recommended in this case to control the concentration of lithium in the blood serum.

Inhibitors of the synthesis of endogenous prostaglandins (eg, NSAIDs)

In some patients, these drugs can reduce the effects of thiazide diuretics.

Other diuretics and antihypertensives

Hydrochlorothiazide, which is a part of the preparation of Firmast® ND 300,can potentiate the effects of other antihypertensive agents, especially ganglion blockers and beta-adrenoreceptor blockers. Hydrochlorothiazide can interact with diazoxide, while their simultaneous application should monitor the concentration of glucose in the blood, serum concentration of uric acid and blood pressure.

FROM non-depolarizing muscle relaxants (tubocurarine), local anesthetic agents, general anesthetics and premedication means before general anesthesia

Effects of nondepolarizing muscle relaxants (eg, tubocurarine), local anesthetic agents, general anesthetics and premedication means before general anesthesia may be potentiated with hydrochlorothiazide and dosage adjustment may be required. When used simultaneously with hydrochlorothiazide, local anesthetics, general anesthetics and premedication means before general anesthesia should be used in reduced doses. If possible, hydrochlorothiazide should be discontinued one week prior to surgery.

Carbamazepine

The simultaneous use of carbamazepine and hydrochlorothiazide may be associated with the risk of developing hyponatremia with clinical manifestations. It is necessary to control the content of electrolytes in the blood serum during the simultaneous use of these drugs. If it is necessary to use carbamazepine, diuretics with a different mechanism of action are recommended, if possible.

Glucocorticosteroids, adrenocorticotropic hormone

Increased risk of hypokalemia.

Catecholamines (for example, norepinephrine [noradrenaline])

The effect of catecholamines may be weakened by the effect of thiazide diuretics. Anticholinergic drugs (eg, atropine, biperidene) Increase in bioavailability of diuretics of the thiazidium series due to slowing down the motility of the gastrointestinal tract.

Cyclophosphamide, methotrexate

Thiazides can reduce the release of cytotoxic drugs by the kidneys and enhance their mielosupressive effects.

Special instructions:

Excessive reduction in blood pressure - patients with hypovolaemia

The use of the drug Firmast® ND-300 has until now rarely been accompanied by an excessive decrease in blood pressure in patients with AH without other risk factors for the development of excessive blood pressure lowering.Excessive reduction in blood pressure, accompanied by clinical symptoms, may develop in patients with hyponatremia / hypovolemia. Hypovolemia and / or hyponatremia should be adjusted before starting the drug Firmast® ND 300. Thiazide diuretics can potentiate the action of other antihypertensive agents (see the sections "With caution" and "Dosage and administration", "Interaction with other drugs").

Impaired kidney and liver function

The drug Firmast® ND 300 is not recommended for patients with severe renal failure (QC < 30 ml / min) (see the section "Contraindications"). In patients with impaired renal function, an increase in azotemia may be associated with the content of hydrochlorothiazide in the formulation. There are no clinical data on the use of the drug in patients who have recently undergone a kidney transplant. When the drug Firmast® ND 300 is used in patients with impaired renal function, periodic monitoring of potassium, creatinine and serum uric acid concentrations is recommended.

The drug Firmast® ND 300 should be used with caution in patients with impaired liver function or progressive liver disease,since even small changes in the water-electrolyte balance can provoke the development of the hepatic coma.

Violations of the water-electrolyte balance and metabolic disturbances

Thiazides, including hydrochlorothiazide, can cause a violation of the water-electrolyte balance (hypokalemia, hyponatremia and hypochloraemic alkalosis). Although the use of thiazide diuretics in monotherapy, especially in high doses, may lead to hypokalemia, simultaneous administration of irbesartan may reduce hypokalemia caused by hydrochlorothiazide. Conversely, due to irbesartan, which is a part of the preparation of Firmast® ND 300, hyperkalemia can occur, especially in the presence of renal failure, heart failure, diabetes mellitus. Regular monitoring of serum potassium in patients at risk is recommended. Potassium-sparing diuretics containing potassium salt substitutes should be used with caution in conjunction with the drug Firmast® ND 300 (see section "Interactions with other drugs"). Deficiency of chloride in serum usually is insignificant and, as a rule, does not require treatment.Thiazides decrease the excretion of calcium by the kidneys and cause a non-permanent and insignificant increase in the serum calcium level. The development of clinically significant hypercalcemia may indicate the possibility of the patient having hyperparathyroidism. Admission of thiazides should be discontinued before the study of parathyroid function. It has been demonstrated that thiazides increase the excretion of magnesium by the kidneys, which can lead to the development of hypomagnesemia. In the treatment of thiazide diuretics, hyperglycemia and exacerbation of gout in some patients may develop. In the treatment of thiazide diuretics, the need for insulin in patients with diabetes mellitus may increase, and the manifestation of latent diabetes mellitus is possible. Treatment with thiazide diuretics was associated with an increase in the concentration of cholesterol and triglycerides in serum. With thiazide diuretics, hyperuricemia or exacerbation of the gout current may occur in some patients. Patients at risk of developing water-electrolyte imbalance and metabolic disorders may need to monitor laboratory indicators.

Systemic lupus erythematosus

It has been reported that the course of systemic lupus erythematosus is exacerbated or worsened with thiazide diuretics.

Acute myopia and secondary acute closed angle glaucoma

Sulfanilamides or sulfonamide derivatives can cause idiosyncratic reactions leading to the development of transient myopia and acute closed-angle glaucoma. Although hydrochlorothiazide is a derivative of sulfonamide, so far only cases of development of acute closed-angle glaucoma have been reported without establishing a causal relationship with its administration. Symptoms of acute closed-angle glaucoma are: acute reduction in visual acuity or eye pain, usually occurring within a period of several hours to several weeks after starting the drug. Left with no treatment acute acute angle glaucoma can lead to persistent loss of vision. If these symptoms occur, stop taking the drug as soon as possible. If it does not manage to normalize intraocular pressure, then urgent therapeutic or surgical treatment may be required.Risk factors for the development of acute angle-closure glaucoma are the indication of anamnesis for allergic reactions to sulfonamides and penicillins.

Double blockade of RAAS with simultaneous application of the drug Firmast ND 300 with ACE inhibitors or with aliskirenom

Double blockade of RAAS with the combination of the drug Firmast® ND 300 with ACE inhibitors or aliskiren is not recommended, as compared to monotherapy, there is an increased risk of a sharp decrease in blood pressure, the development of hyperkalemia and renal dysfunction.

The use of the drug Firmast® ND 300 in combination with aliskiren is contraindicated in patients with diabetes mellitus or renal insufficiency with GFR <60 ml / min / 1.73 m² body surface area) (see "Contraindications", "Interaction with other drugs") and is not recommended in other patients.

Simultaneous use of the drug Firmast ® ND 300 with ACE inhibitors is contraindicated in patients with diabetic nephropathy (see the sections "Contraindications", "Interaction with other drugs") and is not recommended in other patients.

Patients with the function of the nights, depending on the activity of the RAAS

As a consequence of inhibition of RAAS, impairment of renal function in predisposed patients can be expected. In patients with renal function, depending on the activity of RAAS (patients with AH and stenosis of the renal artery of one or both kidneys, patients with CHF III and IV functional class [by classification NYHA]), treatment with drugs that affect RAAS, was associated with oliguria and / or progressive azotemia and rarely with acute renal failure and / or death. It is impossible to exclude the possibility of occurrence of similar effect in the application of APA II, including the preparation of Firmast® ND 300. Patients after sympathectomy

In patients after sympathectomy, the antihypertensive effect of thiazide diuretics may increase.

Stenosis of the aortic aorta and stenosis of the mitral valve, GOKMP

Special care is required when using such vasodilators in such patients, including the preparation of Firmast® ND 300.

Primary hyperaldosteronism

The use of the drug Firmast® ND 300 is inadvisable, since such patients usually do not respond to antihypertensive drugs that affect RAAS.

Anti-doping test

Hydrochlorothiazide can give a positive result in doping control.

Patients with a history of allergic anamnesis or bronchial asthma

Development of allergic reactions to hydrochlorothiazide more likely in patients with a history of allergic anamnesis or in patients with bronchial asthma.

Effect on the ability to drive transp. cf. and fur:The effect of the drug Firmast® ND 300 on the ability to drive vehicles or engage in other potentially hazardous activities requiring increased attention and high speed of psychomotor reactions has not been studied. However, based on its pharmacodynamic properties, the preparation of Firmast® ND 300 should not affect the ability to drive vehicles and engage in other potentially hazardous activities (work at altitude, the work of an air traffic controller, work with mechanisms, etc.). However, when practicing potentially hazardous activities, care should be taken (due to the possibility of developing dizziness, weakness and, in this connection, reducing attention and slowing the speed of psychomotor reactions, see the "Side effect" section).

Form release / dosage:

Tablets, film-coated, 25 mg + 300 mg.

Packaging:7 or 10 tablets are placed in a blister of a combined material polyamide / aluminum foil / PVC-aluminum foil (OPA / Al / PVC-Al). For 2, 4, 8 or 12 blisters (a blister for 7 tablets) or 3, 6, 9 or 10 blisters (a blister of 10 tablets) in a pack of cardboard along with instructions for use.

Storage conditions:At temperatures not higher than 30 ° C, in the original packaging. Keep out of the reach of children.

Shelf life:

5 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-003278

Date of registration:27.10.2015

Date of cancellation:2020-10-27

The owner of the registration certificate:KRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO

Manufacturer: & nbsp

KRKA, dd, Novo mesto, AO Slovenia

Representation: & nbspKRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO

Information update date: & nbsp16.12.2015

Illustrated instructions

Instructions

Firma ND 300 (Firmasta® НD 300)