Firma N 150 - instructions for use, dose, side effects, contraindications

mannitol 73.29 mg, sodium carboxymethyl starch (type A) 45.00 mg, low-substituted giprolose (LH-21) 30.00 mg, talc 27.00 mg, macrogol 6000 12.00 mg, giprolose 20.00 mg, castor oil hydrogenated 8.00 mg

Film sheath:

* Foam 85F34353 II Pink 12.00 mg

* Foam 85F34353 II pink: polyvinyl alcohol 4.80 mg, titanium dioxide (E171) 2.95 mg, macrogene 2.42 mg, talc 1.78 mg, ferric oxide yellow oxide (E172) 0.030 mg, ferric oxide red oxide (E172) 0.019 mg

Description:

Oval biconvex tablets covered 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® N 150 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 (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, regardless of the source or route of its synthesis, including,its pronounced vasoconstrictive and aldosteronosecreting 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 AT₁-receptors 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 AT₁- 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 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 plasma renin activity (APP) blood and the secretion of aldosterone, 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 is independent of age,

race or gender. General antihypertensive response to combination of y

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 orally, the diuretic effect occurs within the first

2 hours, diuresis reached a maximum in about 4 hours and lasted about 6-12 hours.

A significant advantage of the antihypertensive effect of the combination was noted

irbesartan / hydrochlorothiazide (in doses from 12.5 / 150 mg to 25/300 mg) as an initial

therapy in patients with moderate and severe severity of hypertension, compared with

use as an initial therapy of monotherapy with irbesartan (in doses from 150 mg up 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 the drug Firmast® H 150, the absolute bioavailability of irbesartan is 60-80%, and hydrochlorothiazide - 50-80%. Eating does not affect the bioavailability of the active substances of the drug. After taking the drug Firmast® H 150 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 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. The mean values of the plasma half-life period (T_1/2) of hydrochlorothiazide are 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 (compared with men), slightly higher plasma concentrations of irbesartan are noted. However, gender-related differences 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_max 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-Pyo scale) and moderately expressed (functional class B 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_maxirbesartan 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 preparation of Firmas® H 150 (see the "Composition" section) or to other sulfonamide derivatives (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 body surface area).

- 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 NYMA 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® H 150 during pregnancy, as well as any other drug that directly affects 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® N 150, 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® N 150 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® H 150.

Dosing and Administration:

The preparation of Firmast® H 150 is taken once a day, regardless of the time of ingestion.

The drug Firmast® H 150 should be used in patients whose blood pressure is not adequately controlled by irbesartan or hydrochlorothiazide in monotherapy. Preparation Firmast® H 150 (tablets containing hydrochlorothiazide 12.5 mg and irbesartan 150 mg) can be used in patients in whom blood pressure is not adequately controlled by monotherapy with hydrochlorothiazide or irbesartan 150 mg / day. Maximum daily dose: 2 tablets of the preparation of Firmas® H 150 (tablets containing hydrochlorothiazide 12.5 mg and irbesartan 150 mg) or 1 tablet of Firmast® ND 300.

If it is not possible to achieve the target values of BP with therapy only with the drug Firmast® N 150, then the reception of other antihypertensive medications (for example, beta-blockers and slow calcium channel blockers (BCCC)) can be added to its reception.

As an initial therapy in patients who are supposed to be on the basis of the severity of their disease, they will need to perform a combined antihypertensive

therapy, treatment is started with the drug Firmast® 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 irbesartan / hydrochlorothiazide combination in the pediatric and adolescent patients have not been established.

Elderly patients

Usually, elderly patients do not need a dose reduction. Patients who received the combination of irbesartan / hydrochlorothiazide in clinical trials, in general, there was no difference between the efficacy and safety of patients aged 65 years or 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. Due to the presence should be particularly careful when using the drug in patients with severe hepatic insufficiency as part of the preparation of hydrochlorothiazide (more than 9 points but the scale of Child-Pugh).

Patients with renal insufficiency

Usually in patients with renal insufficiency (mild to moderate severity

- CK> 30 ml / min) dose reduction is not required. However, in connection with the presence in the composition of the drug Firmas® H 150 hydrochlorothiazide in patients with severe renal failure, the use of the drug Firmast® N 150 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 hyponatraemia should be corrected before the application of Finasta® H 150 (see section "Special instructions").

Side effects:

The following undesirable phenomena (AEs) are presented in accordance with the following grades of their incidence and 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 trials of AE in patients who received a combination of irbesartan / hydrochlorothiazide for 6 months and one year or more,were usually moderately expressed and transient, and their frequency was not related to the magnitude of 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 skeleton-muscle 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 moderate to severe arterial hypertension (mean diastolic blood pressure (DBP), sitting at 90-110 mm Hg), the types and frequency of AE observed in patients treated with irbesartan / hydrochlorothiazide as an initial therapy were similar to the AE profile in patients who received initial treatment as monotherapy with irbesartan 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, irbesartan monotherapy 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, irbesartan monotherapy and hydrochlorothiazide monotherapy 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-mentioned AE for the combination irbesartan / hydrochlorothiazide and irbesartan was, respectively: 0% and 0% - for the syncopal state; 0.6% and 0% for excessive LD reduction, 3.6% and 4.0% for dizziness, 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, gastric mucosal irritation, diarrhea, constipation, jaundice (associated with intrahepatic cholestasis), pancreatitis, sialadenitis, vertigo, paresthesia, xantopsy, leukopenia, neutropenia / agranulocytosis , thrombocytopenia, aplastic anemia, hemolytic anemia, photosensitivity reactions, fever, urticaria, necrotizing angiitis (vasculitis, cutaneous vasculitis), respiratory distress syndrome (including pneumonia um and pulmonary edema), anaphylactic reactions, toxic epidermal necrolysis, hyperglycemia, glycosuria, hyperuricemia, disorders of water and electrolyte balance (including hyponatremia and hypokalemia), renal failure, interstitial nephritis, muscle spasms,weakness, anxiety, transient impairment of visual acuity.

Overdose:Symptoms

The most common symptoms observed in adults with an overdose of hydrochlorothiazide were symptoms caused by water-electrolyte disorders of the 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. When an overdose of the drug Firmast®H 150, excessive decrease in blood pressure, the development of bradycardia and tachycardia may occur.

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 data from studies in conditions in vitro, no interaction of irbesartan with drugs metabolized by isoenzymes is expected CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2E1 or CYP3A4. Irbesartan, in general, is metabolized by isofermenga CYP2C9 and, to a lesser extent, undergoes glucuronation. 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.

Medicines containing aliskiren

Combination of the drug Firmast®H 150 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").

Inhibitors of AG1F

The use of the drug Firmast®H 150 simultaneously with ACE inhibitors is contraindicated in patients with diabetic hephopathy and is not recommended in other patients (see the sections "Contraindications", "With caution", "Special instructions").

Drugs affecting the potassium content of serum

Based on the experience gained with the use of other drugs that affect RAAS, with the simultaneous use of potassium preparations; substitutes for salt containing potassium; potassium-sparing diuretics, or others capable of increasing potassium levels in the blood serum of medicines (eg, heparin), it is possible to increase the potassium content in the blood serum. It is necessary to control the potassium content in the blood serum during therapy with the drug Firmast® N 150. Simultaneous with irbesartan hydrochlorothiazide intake can reduce the frequency of this effect.

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

In elderly patients, patients with hypovolemia or patients with impaired renal function, the use of NSAIDs, including COX-2 inhibitors, concomitantly 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 administration of the drug Firmast® H 150 and antidotal drugs, correction of doses of antidotal drugs may be required, since with the intake of hydrochlorothiazide, an increase in serum uric acid concentrations is possible.

Cardiac glycosides, antiarrhythmics

With their simultaneous use with the drug Firmast® N 150 in the case of hypokalemia and hypomagnesemia, caused by the thiazide diuretic entering into its composition, 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 is necessary to divide the time of taking the preparation of Firmas⁴ I I 150 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. Caution should be exercised when using the drug Firmast® H 150 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 part of the preparation of Firmast® N 150, 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

The effects of nondepolarizing muscle relaxants (eg, tubocurarine), local anesthetic agents,means for general anesthesia and means for premedication before general anesthesia may be potentiated with hydrochlorothiazide and correction of their dosage regimen 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 action of catecholamines can be weakened by the influence of thiazide diuretics. Anticholinergic drugs (eg, atropine, biperidene)

Increased bioavailability of thiazide diuretics 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® H 150 to date has rarely been accompanied by excessive reduction in blood pressure in patients with AH without other risk factors for the development of excessive BP reduction. Excessive reduction in blood pressure, accompanied by clinical symptoms, may develop in patients with hyponatremia / hypovolemia. Hypovolemia and / or hyponatremia should be corrected before starting the preparation of Firmasm® H 150. Thiazide diuretics can potentiate the action of other antihypertensive agents (see the sections "With caution" and "Method of administration and dose", "Interaction with other drugs").

Impaired kidney and liver function

Preparation Firmast® N 150 is not recommended for patients with severe renal failure (QC < 30 ml / min.) (See FIG.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® N 150 is used in patients with impaired renal function, periodic monitoring of potassium, creatinine and serum uric acid concentrations is recommended.

The drug Firmast® H 150 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 trigger the development of the hepatic coma.

Violations of the water-electrolyte balance and metabolic disturbances

Thiazides, including hydrochlorothiazide, can cause a violation of 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.On the contrary, due to irbesartan, which is a part of the preparation of Firmast® N 150, 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 preparation of Firmas® H 150 (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 may increase the need for insulin in patients with diabetes, and perhaps a manifestation of latent diabetes. Treatment with thiazide diuretics was associated with an increase in the concentration of cholesterol and triglycerides in the blood serum, but the dose of 12.5 mg contained in the preparation of Firmast® H 150 had virtually no effect on serum cholesterol and triglyceride concentrations. 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 penicilliys.

Double blockade of RAAS with simultaneous application of the preparation of Firmas® H 150 with ACE inhibitors or with aliskiren

Double blockade of RAAS when using the combination of the drug Firmast® H 150 with ACE inhibitors or aliskiren is not recommended,hack as in comparison with monotherapy there is an increased risk of a sharp decline in blood pressure, the development of hyperkalemia and impaired renal function.

The use of the drug Firmast® H 150 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® N 150 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 renal function, depending on the activity of 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 is associated with oliguria and / or progressive azotemia and rarely with acute renal failure and / or death.It is impossible to exclude the possibility of such an effect when using APA II, including preparation Фирмаста®Н 150.

Patients after sympathectomy

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

Stenosis of the aorta aperture and stenosis of the mitral valve, GOK MP

Special caution is required when using such patients with vasodilators, including the preparation of Firmast® N 150.

Primary hyperaldosteronism

The use of the drug Firmast® H 150 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 Finasta® H 150 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® N 150 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 connection with this, reducing attention and slowing the speed of psychomotor reactions, see the "Side effect" section).

Form release / dosage:

Tablets, film-coated, 12.5 mg + 150 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-003294

Date of registration:06.11.2015

Date of cancellation:2020-11-06

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 N 150 (Firmasta N 150)