Fosicard H 20mg/12.5mg #28

Instruction for Fosicard H

You can buy Fosicard H here

Structure

1 tablet contains:
active ingredients: hydrochlorothiazide 12.5 mg, sodium fosinopril 20.0 mg;
excipients: lactose monohydrate 101.5 mg, mixture of pigments PB-23601 (includes: titanium dioxide 4.92 mg, lactose monohydrate 0.6 mg, iron dye yellow oxide 0.36 mg, iron dye red oxide 0.12 mg) 6.0 mg, pregelatinized starch (starch 1500) 25.0 mg, croscarmellose sodium 9.0 mg, lactose monohydrate (Tablettoza 80) 120.0 mg, glyceryl dibehenate 6.0 mg, magnesium stearate (traces).

Description

Round, flat tablets of light orange color, engraved with "FH" on one side, marbling is allowed.
Pharmacotherapeutic group: Combined antihypertensive agent (diuretic + ACE inhibitor)

Pharmacodynamics

Hydrochlorothiazide

Hydrochlorothiazide is a thiazide diuretic. The mechanism of action of thiazide diuretics (thiazides) is not fully understood. Thiazides block the reabsorption of sodium and chlorine ions in the distal tubules of the nephron. They have a diuretic (diuretic) effect, increasing the excretion of sodium and chlorine and excretion of water from the body.
As a result of the diuretic action of hydrochlorothiazide, the volume of circulating fluid decreases, as a result of which the activity of renin and the content of aldosterone in the blood plasma increase. This leads to an increase in the excretion of potassium ions in the urine and a decrease in its content in the blood (hypokalemia). Hydrochlorothiazide also increases the excretion of magnesium ions and decreases the excretion of calcium ions in the urine. Thiazide diuretics reduce the excretion of uric acid by the kidneys and increase its content in the blood, and also reduce the activity of carbonic anhydrase by increasing the excretion of bicarbonate ions. These effects are usually mild and do not affect urine pH.
At maximum therapeutic doses, thiazide diuretics have a similar diuretic / natriuretic effect. Usually natriuresis and diuresis occur within 2 hours and reach a maximum after about 4 hours. The duration of the diuretic effect of hydrochlorothiazide is 6 to 12 hours. Along with a diuretic, hydrochlorothiazide in therapeutic doses also has a moderate antihypertensive effect. Thiazide diuretics have no effect on normal blood pressure (BP).

Fosinopril

Fosinopril sodium is the sodium salt of an ester of the pharmacologically active compound fosinoprilat. After entering the body, fosinopril undergoes enzymatic hydrolysis and turns into an active metabolite - fosinoprilat. Fosinoprilat is a specific competitive ACE inhibitor. Due to the inhibition of ACE, it prevents the conversion of inactive angiotensin I into angiotensin II, which has a vasoconstrictor effect and is an active component of the renin-angiotensin-aldosterone system (RAAS) of the body. ACE inhibition leads to a decrease in the concentration of angiotensin II in the blood plasma, which leads to a decrease in its vasopressor activity and a decrease in aldosterone secretion, which leads to a decrease in total peripheral vascular resistance (OPSS) and systemic blood pressure.
By inhibiting the tissue RAS of the heart, fosinopril prevents myocardial hypertrophy and left ventricular dilatation or promotes their reverse development (cardioprotective effect). Increases the activity of the kallikrein-kinin system, stabilizes the level of the vasodilating peptide bradykinin in tissues and blood (its degradation to inactive peptides decreases), increases the release of biologically active substances (PGE2 and PGI2, endothelial relaxing factor, atrial natriuretic factor), which have a natriuretic and vasodilatory effect and improving renal blood flow. Reduces the formation of arginine-vasopressin and endothelin-1, which have vasoconstrictor properties. Reduces systolic and diastolic blood pressure both in the standing position and in the supine position, without causing orthostatic reactions and postural tachycardia. A decrease in blood pressure is not accompanied by a change in the volume of circulating blood (BCC), cerebral and renal blood flow, blood supply to internal organs, skeletal muscles, skin, reflex activity of the myocardium.
After taking fosinopril orally, the antihypertensive effect develops within 1 hour, reaches a maximum after 2-6 hours and lasts 24 hours. Orthostatic hypotension and tachycardia are sometimes noted in patients with hypovolemia or on a salt-free diet. It may take several weeks to achieve maximum therapeutic effect.
The effectiveness of the antihypertensive action of Fosicard H does not depend on age, sex and body weight. Fozinopril does not cause withdrawal symptoms even with abrupt discontinuation of treatment. The antihypertensive effects of fosinopril and thiazide diuretics are complementary.

Pharmacokinetics

The pharmacokinetics of hydrochlorothiazide and fosinopril when taken simultaneously does not differ from that when administered separately.

Hydrochlorothiazide

Absorption and distribution
Hydrochlorothiazide is incomplete, but rather rapidly absorbed from the gastrointestinal tract. After oral administration in a dose of 100 mg, the maximum concentration of hydrochlorothiazide in blood plasma is reached after 1.5-2.5 hours. At the maximum diuretic activity (approximately 4 hours after administration), the concentration of hydrochlorothiazide in the blood plasma is 2 μg / ml. The connection with blood plasma proteins is 40%.
Hydrochlorothiazide crosses the placental barrier and is excreted in breast milk, does not cross the blood-brain barrier.
Metabolism
Hydrochlorothiazide is not metabolized in the human body.
Withdrawal
The primary route of excretion through the kidneys (filtration and secretion) is unchanged. Approximately 61% of an oral dose is eliminated within 24 hours. In patients with normal renal function, the elimination half-life is 5.6 to 14.8 hours (average 6.4 hours).

Pharmacokinetics in special patient groups

Impaired renal function
In patients with moderate renal insufficiency, the half-life of hydrochlorothiazide is on average 11.5 hours, and in patients with creatinine clearance less than 30 ml / min - 20.7 hours.
Fosinopril
After oral administration, the absorption of fosinopril is approximately 30-40%, of which 50-100% is hydrolyzed in the liver to fosinoprilat. The degree of absorption of fosinopril does not depend on food intake, but the rate of absorption may be slowed down. In case of impaired liver function, the rate of its hydrolysis can be slowed down, while the degree of hydrolysis does not change noticeably.
The maximum concentration of fosinoprilat in blood plasma is reached after approximately 3 hours and does not depend on the dose taken. Fozinopril has linear pharmacokinetics. Fosinoprilat binds to a high degree with blood plasma proteins (90-95%) and to a small extent binds to the cellular components of the blood. Has a relatively small volume of distribution. In hypertensive patients with normal renal and hepatic function, the elimination half-life (T1 / 2) of fosinoprilat is approximately 11.5 hours.
Renal failure
In renal failure, absorption, bioavailability and binding of Fosicard H to blood plasma proteins do not change significantly. The total clearance of fosinoprilat in patients with renal insufficiency is almost 50% lower than in patients with normal renal function. Since excretion through the liver with bile partially compensates for the decrease in excretion through the kidneys, the clearance of fosinoprilat does not differ significantly in patients with moderate renal failure from that in patients with severe renal failure. In patients with varying degrees of renal failure, including end-stage renal failure (creatinine clearance (CC) less than 10 ml / min / 1.73 m2), there is a moderate increase in the area under the concentration-time curve (AUC) (less than 2 times compared with that in patients with normal renal function). The clearance of fosinoprilat during hemodialysis and peritoneal dialysis is on average 2% and 7% compared to the clearance of urea.
Liver failure
The degree of hydrolysis of fosinoprilat in patients with alcoholic or biliary cirrhosis decreases insignificantly, despite the fact that the rate of hydrolysis may be reduced. The maximum concentration and AUC of fosinoprilat are higher in patients with hepatic impairment after taking the first dose, however, with the introduction of repeated doses, this difference has no clinical significance.
Indications: Arterial hypertension (for patients for whom combination therapy is indicated).

Contraindications

- Hypersensitivity to hydrochlorothiazide, other sulfonamide derivatives, fosinopril, other ACE inhibitors or any other substance that is part of Fosicard H.
- Hereditary or idiopathic angioedema (including from the use of other ACE inhibitors in history).
- Severe renal failure (CC <30 ml / min / 1.73 m2), anuria.
- Severe hepatic impairment or hepatic encephalopathy (risk of developing hepatic coma).
- Gout.
- Refractory hypokalemia, hyponatremia, hypercalcemia.
- Pregnancy, breastfeeding period.
- Age up to 18 years (efficacy and safety have not been established).
- Simultaneous use with aliskiren and preparations containing aliskiren in patients with diabetes mellitus and / or moderate or severe renal impairment (glomerular filtration rate (GFR) <60 ml / min / 1.73 m2 body surface area).
- Simultaneous use with angiotensin II receptor antagonists (ARA II) in patients with diabetic nephropathy.
- Concomitant use with neutral endopeptidase inhibitors (for example, with preparations containing sacubitrile) due to the high risk of angioedema (see section "Interaction with other medicinal products").
- Rare hereditary galactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome (Fosicard H contains lactose).

Carefully

Arterial hypotension, bilateral renal artery stenosis or stenosis of an artery of a single kidney; renal failure; condition after kidney transplantation; aortic or mitral stenosis; hypertrophic obstructive cardiomyopathy; chronic heart failure III-IV functional class (NYHA classification); ischemic heart disease (CHD); cerebrovascular diseases (including cerebrovascular insufficiency); systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma), inhibition of bone marrow hematopoiesis; immunosuppressive therapy, concomitant use of allopurinol or procainamide, or a combination of these complicating factors (increased risk of neutropenia and agranulocytosis); diabetes; hyperkalemia; simultaneous use with potassium-sparing diuretics, potassium preparations, potassium-containing substitutes for table salt; simultaneous use with lithium preparations; aggravated allergic history or history of angioedema; simultaneous desensitization; simultaneous low-density lipoprotein apheresis using dextran sulfate; simultaneous hemodialysis using high-flow membranes; conditions accompanied by a decrease in the BCC (including diarrhea, vomiting, previous treatment with diuretics, adherence to a diet with limited salt), hyponatremia (risk of dehydration, arterial hypotension, chronic renal failure); use during major surgical interventions or during general anesthesia; use in patients of the black race; use in elderly patients; dysfunction of the liver of mild to moderate severity, progressive liver disease; hypokalemia; hypercalcemia; an increase in the duration of the QT interval on the ECG; the simultaneous use of drugs that can cause polymorphic ventricular tachycardia of the "pirouette" type or increase the duration of the QT interval on the ECG; simultaneous use of lithium preparations, drugs that can cause hypokalemia, cardiac glycosides; history of allergic reactions to penicillin; hyperparathyroidism; hyperuricemia; history of non-melanoma skin cancer (see section "Special instructions").

Pregnancy and lactation

The use of Fosicard H is contraindicated during pregnancy and during breastfeeding.

Pregnancy

Hydrochlorothiazide
There is limited experience with hydrochlorothiazide during pregnancy (especially in the first trimester). Preclinical safety data are insufficient.
Hydrochlorothiazide crosses the placental barrier and is detected in the umbilical cord blood. Taking into account the mechanism of the pharmacological action of hydrochlorothiazide, its use in the second and third trimesters of pregnancy can disrupt placental perfusion and lead to the development of complications such as jaundice, disturbances in water and electrolyte balance and thrombocytopenia in the fetus and newborn. Cases of thrombocytopenia in newborns whose mothers received thiazide diuretics have been described.
The use of hydrochlorothiazide during pregnancy is contraindicated. Hydrochlorothiazide should not be used to treat gestosis in the second half of pregnancy (edema, arterial hypertension or preeclampsia), because it increases the risk of a decrease in BCC and placental hypoperfusion, but does not have a beneficial effect on the course of these complications of pregnancy. Diuretics do not prevent the development of gestosis.
ACE inhibitors (including fosinopril)
The use of ACE inhibitors during the first trimester of pregnancy is not recommended (see section "Special instructions"). The use of ACE inhibitors during the second and third trimesters of pregnancy is contraindicated (see sections "Contraindications" and "Special instructions").
There is no convincing epidemiological evidence of the risk of teratogenic effects of ACE inhibitors during the first trimester of pregnancy; however, a slight increase in risk cannot be ruled out. Except in cases where treatment with ACE inhibitors is considered necessary, patients planning a pregnancy should be switched to alternative antihypertensive pharmacotherapy that has an established safety profile for use during pregnancy. If pregnancy is confirmed, treatment with ACE inhibitors should be discontinued immediately and, if necessary, alternative treatment should be initiated. It is known that therapy with ACE inhibitors during the second and third trimesters of pregnancy has a fetotoxic effect in humans (decreased renal function, oligohydramnios, slowed down ossification of the skull) and toxic effects in the neonatal period (renal failure, hypotension, hyperkalemia). If ACE inhibitors have been exposed since the second trimester of pregnancy, an ultrasound examination of renal function and skull is recommended. Infants whose mothers have taken ACE inhibitors should be closely monitored for hypotension (see Contraindications and Special Instructions).

Breastfeeding period

Hydrochlorothiazide
Hydrochlorothiazide passes into breast milk, and therefore its use during breastfeeding is contraindicated. If the use of hydrochlorothiazide during lactation is absolutely necessary, then breastfeeding should be discontinued.
Fosinopril sodium
Due to the extremely limited information regarding the use of fosinopril sodium during breastfeeding, the drug Fosicard H is not recommended, and alternative therapies with better established safety profiles are preferable, especially in the case of breastfeeding a newborn or premature baby.

Method of administration and dosage

Inside, regardless of the time of the meal, drinking plenty of fluids. The recommended dose is 1 tablet once a day.
The drug Fosicard H is not intended for the initial therapy of arterial hypertension. The dose of the drug Fosicard H is selected after previously titrated doses of monocomponent medicinal products containing the active substances that make up Fosicard H.
If a change in the dose of one of the active substances in the composition of the drug Fosicard H is required (for example, in connection with a newly diagnosed disease, a change in the patient's condition or drug interaction), then an individual selection of doses of individual components is necessary.

Special patient groups

Impaired renal function
In patients with mild to moderate renal impairment (CC> 30 ml / min and <80 ml / min), a gradual increase in the dosage of each of the components is recommended before prescribing Fosicard H. The use of the drug Fosicard H is contraindicated in patients with severe renal impairment (CC <30 mg / min).
Liver dysfunction
No dose adjustment is required in patients with mild to moderate renal impairment. The use of the drug Fosicard H is contraindicated in patients with severe renal failure or hepatic encephalopathy.
Elderly age
No dose adjustment is required.

Side effects

Very often (≥10%)
- hyperglycemia, glucosuria, hyperuricemia, electrolyte imbalance (including hyponatremia), increased cholesterol and triglyceride levels

Often (≥1% - <10%)

- dizziness, headache
- tachycardia, palpitations
- hypotension, orthostatic hypotension
- cough
- nausea, stomach irritation, vomiting, diarrhea, constipation, pancreatitis
- rash, angioedema, dermatitis
- chest pain, weakness
- an increase in the level of alkaline phosphatase, bilirubin, LDH and transaminases
- a reversible increase in the level of creatinine, urea, uric acid

Uncommon (≥0.1% - <1%)

- reversible decrease in hemoglibin and hematocrit
- gout, hyperkalemia
- depression, confusion
- cerebral infarction, paresthesia, drowsiness, stroke, fainting, taste disturbances, sleep disturbances
- visual impairment, xanthopsia
- ear pain, ringing in the ears
- angina pectoris, myocardial infarction and acute cerebrovascular accident, cardiac arrest, rhythm disturbances, conduction disturbances
- hypertension, shock, transient ischemia
- dyspnea, rhinitis, sinusitis, tracheobronchitis
- dry mouth, flatulence
- hyperhidrosis, pruritus, urticaria, photosensitivity reactions
- myalgia
- renal failure, interstitial nephritis, sexual dysfunction
- fever, peripheral edema, sudden death, chest pain
- weight gain
- decreased appetite, anorexia
- respiratory distress syndrome (including pneumonitis and pulmonary edema)
- intrahepatic cholestatic jaundice

Rarely (≥0.01% - <0.1%)

- reversible anemia, eosinophilia, leukopenia, lymphadenopathy, neutropenia
- dysphasia, memory impairment, disorientation
- hot flashes, hemorrhages, peripheral vascular disease
- bronchospasm, epistaxis, laryngitis / hoarseness, pneumonia, pulmonary hyperemia
- oral ulceration, pancreatitis, swelling of the tongue, bloating, dysphagia, hepatitis
- ecchymosis
- arthritis
- dysfunction of the prostate gland
- weakness in the limbs
- hyponatremia, an increase in hemoglobin levels
- sialadenitis
- leukopenia, neutropenia / agranulocytosis, thrombocytopenia, aplastic anemia, hemolytic anemia, bone marrow suppression
- anxiety, sleep disturbance, depression
- vasculitis
- cutaneous lupus-like reactions, reactivation of cutaneous lupus erythematosus, anaphylactic reactions, toxic epidermal necrolysis
- muscle spasm
- impaired renal function

Very rare (≥0.01% - <0.1%)

- agranulocytosis
- angioedema, (partial) intestinal obstruction
- liver failure
- acute renal failure

Overdose

Symptoms

Depending on the degree of overdose, the following symptoms may occur: severe hypotension, bradycardia, circulatory shock, electrolyte imbalance, renal failure, persistent polyuria, depression of consciousness (including coma), convulsions, paresis, heart rhythm disturbances, paralytic intestinal obstruction. The most common manifestations of hydrochlorothiazide overdose are increased urine output, accompanied by acute fluid loss (dehydration) and electrolyte disturbances (hypokalemia, hyponatremia, hypochloremia).
An overdose of hydrochlorothiazide can manifest with the following symptoms:
- on the part of the cardiovascular system: tachycardia, decreased blood pressure, shock;
- on the part of the nervous system: weakness, confusion, dizziness and spasms of the calf muscles, paresthesia, impaired consciousness, fatigue;
- from the gastrointestinal tract: nausea, vomiting, thirst;
- on the part of the kidneys and urinary tract: polyuria, oliguria or anuria (due to hemoconcentration).
Laboratory indicators: hypokalemia, hyponatremia, hypochloremia, alkalosis, increased blood urea nitrogen (especially in patients with renal failure).

Treatment

In case of an overdose, symptomatic and supportive therapy is performed. Recommended treatment for overdose is intravenous infusion of saline. In case of an overdose after oral administration, patients should be closely monitored, preferably in an intensive care unit. Serum electrolyte and creatinine levels should be monitored frequently. Recommended measures include induction of vomiting and / or gastric lavage, as well as correcting dehydration, electrolyte imbalance, and hypotension using standard methods.
With recent ingestion, to prevent absorption and accelerate excretion, it is necessary to wash the stomach, prescribe sorbents and sodium sulfate within 30 minutes after taking fosinopril.
If hypotension occurs, the patient should be placed in a position with raised legs and the loss of fluid and salts should be urgently replenished.
Bradycardia or widespread vagal reactions should be treated with atropine. A decision may be made to use a pacemaker. Fosinopril is not removed from the body during dialysis.
If Fosicard H has been recently taken, induction of vomiting or gastric lavage is indicated to eliminate hydrochlorothiazide. The absorption of hydrochlorothiazide can be reduced by ingestion of activated carbon.
In case of a decrease in blood pressure or shock, the volume of circulating blood should be replenished with the introduction of plasma-substituting fluids and a deficiency of electrolytes (potassium, sodium).
In case of respiratory disorders, oxygen inhalation or artificial ventilation of the lungs is indicated.
It is necessary to monitor the water and electrolyte balance (especially the potassium content in the blood serum) and kidney function until they are normalized.
There is no specific antidote. Hydrochlorothiazide is excreted by hemodialysis, but the extent of its excretion has not been established.

Interaction

Hydrochlorothiazide

Combinations of drugs that are not recommended
Lithium preparations
With the simultaneous use of hydrochlorothiazide and lithium preparations, the renal clearance of lithium decreases, which can lead to an increase in the concentration of lithium in the blood plasma and an increase in its toxicity. If the simultaneous use of hydrochlorothiazide is necessary, the dose of lithium preparations should be carefully selected, the concentration of lithium in the blood plasma should be regularly monitored and the dose of Fosicard H should be appropriately selected.
Combinations of drugs requiring special attention
Drugs that can cause pirouette-type polymorphic ventricular tachycardia
Hydrochlorothiazide should be used with extreme caution simultaneously with drugs such as:
- antiarrhythmic drugs of class IA (quinidine, hydroquinidine, disopyramide, procainamide) and class IC (flecainide);
- Class III antiarrhythmic drugs (dofetilide, ibutilide, bretylium tosylate, sotalol, dronedarone, amiodarone);
- other (non-antiarrhythmic) medicines, such as:
    antipsychotics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine, fluphenazine), benzamides (amisulpride, sultopride, sulpride, tiapride), butyrophenones (droperidol, haloperidol); pimozide, sertindole;
    antidepressants: tricyclic antidepressants, selective serotonin reuptake inhibitors (citalopram, escitalopram);
    antibacterial agents: fluoroquinolones (levofloxacin, moxifloxacin, sparfloxacin, ciprofloxacin); macrolides (intravenous erythromycin, azithromycin, clarithromycin, roxithromycin, spiramycin), co-trimoxazole;
    antifungal agents: azoles (voriconazole, itraconazole, ketoconazole, fluconazole);
    antimalarial drugs (quinine, chloroquine, mefloquine, halofantrine, lumefantrine);
    antiprotozoal agents (parenteral pentamidine);
    antianginal agents (ranolazine, bepridil);
    antineoplastic agents (vandetanib, arsenic trioxide, oxaliplatin, tacrolimus);
    antiemetics (domperidone, ondasetron);
    agents affecting the motility of the gastrointestinal tract (cisapride);
    antihistamines (astemizole, terfenadine, mizolastine);
    other medicines (anagrelide, vasopressin, diphemanil methyl sulfate, ketanserin, probucol, propofol, sevoflurane, terlipressin, therodilin, cilostazol).
With simultaneous use with thiazide diuretics, the risk of developing ventricular arrhythmias increases, especially polymorphic ventricular tachycardia of the "pirouette" type (risk factor - hypokalemia).
It is necessary to determine the content of potassium in the blood plasma and, if necessary, adjust it before the start of combination therapy with hydrochlorothiazide with the above drugs. It is necessary to monitor the patient's clinical condition, the content of blood plasma electrolytes and ECG indicators. In patients with hypokalemia, it is necessary to use drugs that do not cause polymorphic ventricular tachycardia of the "pirouette" type.
Medicines that can prolong the QT interval
The simultaneous use of hydrochlorothiazide with drugs that can increase the duration of the QT interval should be based on a careful assessment for each patient of the ratio of the expected benefit and potential risk (there may be an increase in the risk of developing polymorphic ventricular tachycardia of the "pirouette" type). When using such combinations, it is necessary to regularly record an ECG (to detect prolongation of the QT interval), as well as monitor the content of potassium in the blood.
Drugs that can cause hypokalemia: amphotericin B (when administered intravenously), gluco- and mineralocorticosteroids (when used systemically), tetracosactide (ACTH), glycyrrhizic acid (carbenoxolone, drugs containing licorice root), laxatives that stimulate intestinal motility.
Increased risk of hypokalemia with simultaneous use with hydrochlorothiazide (additive effect). Regular monitoring of the potassium content in the blood plasma is necessary, if necessary, its correction. Against the background of hydrochlorothiazide therapy, it is recommended to use laxatives that do not stimulate intestinal motility.
Cardiac glycosides
Hypokalemia and hypomagnesemia caused by the action of thiazide diuretics increase the toxicity of cardiac glycosides. With the simultaneous use of hydrochlorothiazide and cardiac glycosides, the concentration of potassium in the blood plasma, ECG parameters should be regularly monitored, and, if necessary, the therapy should be adjusted.
Drug combinations requiring attention
Other antihypertensive drugs
Potentiation of the antihypertensive action of hydrochlorothiazide (additive effect). It may be necessary to adjust the dose of simultaneously prescribed antihypertensive drugs.
It is recommended to stop taking hydrochlorothiazide 2-3 days before starting therapy with ACE inhibitors to prevent the development of symptomatic arterial hypotension. If this is not possible, then the initial dose of ACE inhibitors should be reduced.
Ethanol, barbiturates, antipsychotics (neuroleptics), antidepressants, anxiolytics, narcotic analgesics and general anesthetics
It is possible to enhance the antihypertensive effect of hydrochlorothiazide and potentiate orthostatic hypotension (additive effect).
Non-depolarizing muscle relaxants (eg, tubocurarine)
It is possible to enhance the effect of non-depolarizing muscle relaxants.
Adrenomimetics (pressor amines)
Hydrochlorothiazide may reduce the effect of adrenergic agonists such as epinephrine (adrenaline) and norepinephrine (norepinephrine).
Non-steroidal anti-inflammatory drugs (NSAIDs), including selective cyclooxygenase-2 (COX-2) inhibitors and high-dose acetylsalicylic acid (≥ 3 g / day)
NSAIDs can reduce the diuretic and antihypertensive effects of hydrochlorothiazide. With simultaneous use, there is a risk of developing acute renal failure due to a decrease in the glomerular filtration rate. Hydrochlorothiazide may increase the toxic effect of high doses of salicylates on the central nervous system.
Oral hypoglycemic agents
Thiazide diuretics affect glucose tolerance (hyperglycemia may develop) and reduce the effectiveness of hypoglycemic agents (dose adjustment of hypoglycemic agents may be required).
Care should be taken to co-use hydrochlorothiazide and metformin due to the risk of lactic acidosis in the presence of hydrochlorothiazide-induced renal dysfunction.
Beta-blockers, diazoxide
The simultaneous use of thiazide diuretics (including hydrochlorothiazide), with beta-blockers or diazoxide may increase the risk of hyperglycemia.
Medicines used to treat gout (probenecid, sulfinpyrazone, allopurinol)
Dose adjustment of uricosuric drugs may be required, since hydrochlorothiazide increases the concentration of uric acid in the blood serum. Thiazide diuretics may increase the incidence of hypersensitivity reactions to allopurinol.
Cytotoxic (antineoplastic) drugs
Thiazide diuretics reduce renal excretion of cytotoxic drugs (eg, cyclophosphamide and methotrexate) and potentiate their myelosuppressive effects.
Cyclosporine
With the simultaneous use of thiazide diuretics and cyclosporine, the risk of developing hyperuricemia and exacerbation of gout increases.
Oral anticoagulants
Thiazide diuretics may reduce the effect of oral anticoagulants.
Iodine contrast agents
Dehydration of the body while taking thiazide diuretics increases the risk of developing acute renal failure, especially when using high doses of iodine-containing contrast agents. Before using iodine-containing contrast media, it is necessary to compensate for the loss of fluid.
Calcium preparations
With simultaneous use, it is possible to increase the calcium content in the blood and the development of hypercalcemia due to a decrease in the excretion of calcium ions by the kidneys. If the simultaneous administration of calcium-containing drugs is necessary, then the calcium content in the blood plasma should be monitored and the dose of calcium preparations should be adjusted.
Anionic exchange resins (cholestyramine and colestipol)
Anionic exchange resins reduce the absorption of hydrochlorothiazide. Single doses of colestyramine and colestipol reduce the absorption of hydrochlorothiazide in the gastrointestinal tract by 85% and 43%, respectively.
Fosinopril
Double blockade of RAAS
In the literature, it was reported that in patients diagnosed with atherosclerotic disease, heart failure or diabetes mellitus with damage to target organs, double blockade of the RAAS with the use of angiotensin II receptor antagonists (ARA II), ACE inhibitors or aliskiren (direct renin inhibitor) is associated with an increased frequency the development of arterial hypotension, fainting, hyperkalemia and impaired renal function (including acute renal failure), when compared with the use of a single drug that affects the RAAS. Double blockade (for example, the appointment of ACE inhibitors with ARA II or aliskiren) should be carried out only in certain specific situations, regularly monitoring kidney function.
The simultaneous use of ACE inhibitors with drugs containing aliskiren is contraindicated in patients with diabetes mellitus and / or with moderate or severe renal failure (GFR less than 60 ml / min / 1.73 m2 of body surface area) and is not recommended in other patients.
The simultaneous use of ACE inhibitors with ARA II is contraindicated in patients with diabetic nephropathy and is not recommended in other patients.
Potassium-sparing diuretics, potassium preparations, potassium-containing substitutes for table salt and other drugs that can increase serum potassium
Potassium preparations, potassium-sparing diuretics (amiloride, spironolactone, eplerenone, triamterene), potassium preparations, potassium-containing substitutes for table salt and other drugs that can increase serum potassium (including angiotensin II receptor antagonists, heparin, tacrolimus, cyclosporin containing co-trimoxazole [trimethoprim + sulfamethoxazole]) increase the risk of developing hyperkalemia.
In patients with chronic heart failure, diabetes mellitus, who are simultaneously taking potassium-sparing diuretics, potassium, potassium-containing salt substitutes, or other drugs that cause hyperkalemia (for example, heparin), ACE inhibitors increase the risk of hyperkalemia.
Potassium-sparing (thiazide and "loop") diuretics
With the simultaneous use of fosinopril with diuretics, especially at the beginning of diuretic therapy, as well as in combination with a strict diet that limits sodium intake, or with hemodialysis, a pronounced decrease in blood pressure may develop, especially in the first hour after taking the initial dose of fosinopril.
Other antihypertensive drugs
Antihypertensive drugs, opioid analgesics, drugs for general anesthesia enhance the antihypertensive effect of fosinopril.
Lithium preparations
In patients receiving fosinopril concomitantly with lithium preparations, it is possible to increase the concentration of lithium in the blood plasma and the risk of developing lithium intoxication (careful monitoring of the lithium content in the blood plasma is recommended).
NSAIDs, including selective cyclooxygenase-2 (COX-2) inhibitors and high-dose acetylsalicylic acid (≥ 3 g / day)
It is known that indomethacin and other NSAIDs, incl. selective COX-2 inhibitors and acetylsalicylic acid at a dose exceeding 3 g per day can reduce the antihypertensive effect of ACE inhibitors, especially in patients with low-rootin arterial hypertension. In patients over 65 years of age, with hypovolemia (including during treatment with diuretics), with impaired renal function, the simultaneous administration of NSAIDs, including selective COX-2 inhibitors and ACE inhibitors (including fosinopril) can lead to deterioration of function kidney, up to acute renal failure. This condition is usually reversible. Renal function should be closely monitored in patients taking fosinopril and NSAIDs.
Hypoglycemic drugs
Fosinopril enhances the hypoglycemic effect of sulfonylurea derivatives, insulin.
Allopurinol, procainamide, cytostatics, immunosuppressants, glucocorticosteroids (with systemic use)
Fozinopril increases the risk of leukopenia / agranulocytosis when used simultaneously with allopurinol, cytostatic agents, immunosuppressants, procainamide.
MTOR (mammalion Target of Rapamycin) inhibitors (eg, temsirolimus, sirolimus, everolimus)
In patients taking simultaneously ACE inhibitors and mTOR inhibitors (temsirolimus, sirolimus, everolimus), there was an increase in the incidence of angioedema.
Type IV dipeptidyl peptidase (DPP-IV) inhibitors (gliptins), e.g. sitagliptin, saxagliptin, vildagliptin, linagliptin
In patients taking simultaneously ACE inhibitors and type IV dipeptidyl peptidase inhibitors (gliptins), an increase in the incidence of angioedema was observed.
Neutral endopeptidase inhibitors (NEP)
An increased risk of angioedema has been reported with concomitant use of ACE inhibitors and racecadotril (an enkephalinase inhibitor used to treat acute diarrhea).
With the simultaneous use of ACE inhibitors with drugs containing sacubitril (neprilisin inhibitor), the risk of developing angioedema increases, and therefore the simultaneous use of these drugs is contraindicated. ACE inhibitors should be prescribed no earlier than 36 hours after discontinuation of drugs containing sacubitrile. The appointment of drugs containing sacubitril is contraindicated in patients receiving ACE inhibitors, as well as within 36 hours after discontinuation of ACE inhibitors.
Tissue plasminogen activators
Observational studies revealed an increased incidence of angioedema in patients taking ACE inhibitors after using alteplase for thrombolytic therapy of ischemic stroke.
Pharmacokinetic interactions
The simultaneous use of antacids (including aluminum or magnesium hydroxide), as well as the carminative agent simethicone can reduce the absorption of fosinopril, so these drugs should be taken at intervals of at least 2 hours).

Special instructions

The use of the drug Fosicard H in patients with acute myocardial infarction is not recommended due to insufficient experience in clinical use and should not be used to relieve hypertensive crisis.

Hydrochlorothiazide

Renal dysfunction
In patients with impaired renal function, hydrochlorothiazide may cause azotemia. With renal failure, accumulation of hydrochlorothiazide is possible.
In patients with reduced renal function, periodic monitoring of creatinine clearance is necessary. With the progression of renal dysfunction and / or the onset of oliguria (anuria), hydrochlorothiazide should be discontinued.
Liver dysfunction
When using thiazide diuretics in patients with impaired liver function, hepatic encephalopathy may develop. The use of thiazides is contraindicated in patients with severe hepatic impairment or hepatic encephalopathy. In patients with mild to moderate hepatic impairment and / or progressive liver disease, hydrochlorothiazide should be used with caution, since even a small change in the water-electrolyte balance and the accumulation of ammonium in the blood serum can cause hepatic coma. If symptoms of encephalopathy appear, diuretics should be discontinued immediately.
Water and electrolyte balance and metabolic disorders
Thiazide diuretics (including hydrochlorothiazide) can cause a decrease in BCC (hypovolemia) and disturbances in water and electrolyte balance (including hypokalemia, hyponatremia, hypochloremic alkalosis). Clinical symptoms of imbalance in water and electrolyte balance are dry mouth, thirst, weakness, lethargy, fatigue, drowsiness, anxiety, muscle pain or cramps, muscle weakness, marked decrease in blood pressure, oliguria, tachycardia, arrhythmia, and gastrointestinal disorders ( such as nausea and vomiting). In patients receiving hydrochlorothiazide therapy (especially with prolonged course of treatment), clinical symptoms of imbalance in water and electrolyte balance should be monitored regularly to monitor the content of electrolytes in the blood.
Sodium
All diuretic drugs can cause hyponatremia, sometimes leading to severe complications. Hyponatremia and hypovolemia can lead to dehydration and orthostatic hypotension. The concomitant decrease in chlorine ions can lead to secondary compensatory metabolic alkalosis, however, the frequency and severity of this effect are insignificant. It is recommended to determine the content of sodium ions in the blood plasma before starting treatment and regularly monitor this indicator while taking hydrochlorothiazide.
Potassium
When using thiazide and thiazide-like diuretics, there is a risk of a sharp decrease in plasma potassium and the development of hypokalemia (potassium concentration less than 3.4 mmol / l). Hypokalemia increases the risk of developing cardiac arrhythmias (including severe arrhythmias) and enhances the toxic effect of cardiac glycosides. In addition, hypokalemia (as well as bradycardia) is a condition that contributes to the development of polymorphic ventricular tachycardia of the “pirouette” type, which can be fatal.
Hypokalemia poses the greatest danger for the following groups of patients: elderly people, patients simultaneously receiving therapy with antiarrhythmic and non-antiarrhythmic drugs that can cause polymorphic ventricular tachycardia of the "pirouette" type or increase the duration of the QT interval on the ECG, patients with impaired liver function, coronary heart disease , chronic heart failure. In addition, patients with an increased QT interval are at increased risk. It does not matter if this increase is caused by congenital causes or the action of drugs.
In all the cases described above, it is necessary to avoid the risk of developing hypokalemia and regularly monitor the potassium content in the blood plasma. The first measurement of the content of potassium ions in the blood should be carried out within the first week from the start of treatment. If hypokalemia occurs, appropriate treatment should be prescribed. Hypokalemia can be corrected with the use of potassium-containing drugs or the intake of foods rich in potassium (dried fruits, fruits, vegetables).
Calcium
Thiazide diuretics can reduce the excretion of calcium ions by the kidneys, leading to a slight and temporary increase in plasma calcium. In some patients, with long-term use of thiazide diuretics, pathological changes in the parathyroid glands with hypercalcemia and hyperphosphatemia were observed, but without the typical complications of hyperparathyroidism (nephrolithiasis, decreased bone mineral density, peptic ulcer disease). Severe hypercalcemia may be a manifestation of previously undiagnosed hyperparathyroidism. Because of their effect on calcium metabolism, thiazides can affect laboratory parameters of the function of the parathyroid glands. You should stop taking thiazide diuretics (including hydrochlorothiazide) before examining the function of the parathyroid glands.
Magnesium
It has been established that thiazides increase the excretion of magnesium by the kidneys, which can lead to hypomagnesemia. The clinical significance of hypomagnesemia remains unclear.
Glucose
Treatment with thiazide diuretics may impair glucose tolerance. When using hydrochlorothiazide in patients with overt or latent diabetes mellitus, it is necessary to regularly monitor the concentration of glucose in the blood. Dose adjustment of hypoglycemic drugs may be required.
Uric acid
In patients with gout, the frequency of attacks may increase or the course of gout may worsen. Careful monitoring of patients with gout and impaired uric acid metabolism (hyperuricemia) is required.
Lipids
When using hydrochlorothiazide, the concentration of cholesterol and triglycerides in the blood plasma may increase.
Choroidal effusion, acute myopia / secondary angle-closure glaucoma
Hydrochlorothiazide can cause an idiosyncratic reaction, leading to the development of acute myopia and an acute attack of secondary angle-closure glaucoma. Symptoms include a sudden decrease in visual acuity or eye pain, which usually occurs within hours or weeks of starting hydrochlorothiazide therapy. If left untreated, acute angle-closure glaucoma can lead to permanent vision loss. If symptoms appear, it is necessary to stop taking hydrochlorothiazide as soon as possible. If intraocular pressure remains uncontrolled, urgent medical treatment or surgery may be required. Risk factors for the development of acute angle-closure glaucoma are: an allergic reaction to sulfonamides or penicillin in history.
Immune system disorders
There are reports that thiazide diuretics (including hydrochlorothiazide) can cause exacerbation or progression of systemic lupus erythematosus, as well as lupus-like reactions.
In patients receiving thiazide diuretics, hypersensitivity reactions may occur even in the absence of indications of a history of allergic reactions or bronchial asthma.
Photosensitivity
Cases of photosensitivity reactions have been reported when taking thiazide diuretics. If photosensitivity occurs while taking hydrochlorothiazide, treatment should be discontinued.
Non-melanoma skin cancer and lip cancer
In the course of two epidemiological studies based on the Danish National Cancer Registries, an increase in the risk of developing non-melanoma skin cancer and lip cancer (basal cell carcinoma of the skin and squamous cell carcinoma of the skin) was recorded with an increase in the cumulative dose of hydrochlorothiazide.
Hydrochlorothiazide has a photosensitizing effect, which may cause the development of non-melanoma skin and lip cancer.
Patients taking hydrochlorothiazide should be informed about the risk of developing non-melanoma skin and lip cancer and the need for regular skin examinations for new changes as well as changes in existing ones. If any suspicious skin lesions are found, the patient should immediately consult a doctor.
Particular attention should be paid to patients with known risk factors for skin cancer, including: skin phototypes and II (pale and fair skin), family history of skin cancer, history of skin damage caused by sun or ultraviolet radiation and radiation therapy , smoking and taking drugs with photosensitizing effects. Patients should be advised to take skin cancer prevention measures such as limiting sun exposure and exposure to ultraviolet rays, and using appropriate sunscreens when exposed to the sun. Any suspicious skin lesions should be investigated immediately, including histological examination of material obtained by biopsy tissue at the site of damage. It may also be necessary to reconsider the decision on the validity of the use of hydrochlorothiazide in patients who previously had non-melanoma skin cancer and lip cancer.
Athletes
Hydrochlorothiazide may be positive for doping control in athletes.
Other
In patients with severe atherosclerosis of the cerebral and coronary arteries, hydrochlorothiazide should be used with extreme caution.
Thiazide diuretics can reduce the amount of iodine bound to plasma proteins without showing signs of thyroid dysfunction. "

Fosinopril

Arterial hypotension
In patients with an uncomplicated form of arterial hypertension, arterial hypotension may develop in connection with the use of fosinopril. Symptomatic arterial hypotension with the use of ACE inhibitors often develops in patients against the background of intensive diuretic treatment, a diet associated with restriction of sodium chloride, or during dialysis. Transient arterial hypotension is not a contraindication for the use of fosinopril after taking measures to restore the BCC.
In patients with chronic heart failure, treatment with ACE inhibitors can cause an excessive antihypertensive effect, which can lead to oliguria or azotemia and, in rare cases, to fatal acute renal failure. Therefore, when treating chronic heart failure with fosinopril, it is necessary to closely monitor patients, especially during the first 2 weeks of treatment, as well as with any increase in the dose of fosinopril or a diuretic.
It may be necessary to reduce the dose of a diuretic in patients with normal or low blood pressure, who have previously received diuretic therapy or who have hyponatremia.
Arterial hypotension as such is not a contraindication for the further use of fosinopril in chronic heart failure. Some reduction in systemic blood pressure is a common and desirable effect early in chronic heart failure. This decline is greatest in the early stages of treatment and stabilizes within one or two weeks of starting treatment. BP usually returns to baseline without reducing therapeutic efficacy.
Before starting treatment, it is required to analyze the previously conducted antihypertensive therapy, the degree of increase in blood pressure, restriction of the diet for salt and / or fluid and other clinical circumstances. If possible, previous antihypertensive therapy should be discontinued a few days before starting treatment. To reduce the likelihood of arterial hypotension, diuretics should be discontinued 2 to 3 days before starting treatment. Before and during treatment, it is necessary to monitor blood pressure, renal function, the content of potassium ions, creatinine, urea, electrolyte concentrations and the activity of liver enzymes in the blood.
Aortic or mitral stenosis / hypertrophic obstructive cardiomyopathy
Like all drugs with a vasodilating effect, ACE inhibitors should be used with extreme caution in patients with obstruction of the blood outflow from the left ventricle.
Impaired renal function
In patients with arterial hypertension with unilateral or bilateral stenosis of the renal arteries or stenosis of an artery of a single kidney during treatment with ACE inhibitors, the concentration of blood urea nitrogen and serum creatinine may increase. These effects are usually reversible and go away after treatment is stopped. It is necessary to monitor renal function in such patients in the first weeks of treatment. In some patients, an increase in the concentrations of blood urea nitrogen and serum creatinine (usually small and transient) can be observed even without obvious impairment of renal function while using fosinopril and diuretics. A dose reduction of fosinopril may be required.
In patients with severe chronic heart failure, renal function may depend on the activity of the RAAS, therefore, treatment with ACE inhibitors may be accompanied by oliguria and / or progressive azotemia, and in rare cases - to acute renal failure and death.
Kidney transplant
There is no experience with fosinopril in patients who have recently undergone kidney transplantation.
Liver dysfunction
In rare cases, with the use of ACE inhibitors, a syndrome is noted, the first manifestation of which is cholestatic jaundice. This is followed by fulminant necrosis of the liver, sometimes fatal. The mechanism of development of this syndrome has not been studied. With the appearance of noticeable yellowness and a pronounced increase in the activity of liver enzymes, treatment with fosinopril should be discontinued and appropriate treatment should be prescribed.
In patients with impaired liver function, there may be an increased concentration of fosinopril in the blood plasma. In cirrhosis of the liver (including alcoholic), the apparent total clearance of fosinoprilat is reduced, and the AUC is approximately 2 times higher than in patients without liver dysfunction.
Neutropenia / agranulocytosis / thrombocytopenia / anemia
Perhaps the development of agranulocytosis and suppression of bone marrow function during treatment with ACE inhibitors. These cases are more common in patients with impaired renal function, especially in the presence of systemic connective tissue diseases (SLE or scleroderma). Before starting therapy with ACE inhibitors and during treatment, leukocytes and leukocyte counts are determined (once a month in the first 3-6 months of treatment and in the first year of using fosinopril in patients with an increased risk of neutropenia).
Hypersensitivity reactions / angioedema
It was reported about the development of angioedema of the extremities, face, lips, mucous membranes, tongue, pharynx or larynx in patients with the use of fosinopril. Swelling of the tongue, pharynx, or larynx can lead to airway obstruction, which can be fatal. In such cases, it is necessary to stop taking fosinopril and carry out urgent measures, including subcutaneous administration of a solution of epinephrine (adrenaline) (1: 1000), as well as taking other measures of emergency therapy. In most cases of edema of the face, oral mucosa, lips and extremities, discontinuation of fosinopril treatment led to the normalization of the condition; however, sometimes appropriate therapy was required.
Swelling of the intestinal mucosa
While taking ACE inhibitors, swelling of the intestinal mucosa was rarely observed. Patients complained of abdominal pain (with no nausea and vomiting), in some cases, swelling of the intestinal mucosa occurred without facial edema, C1-esterase activity was normal. Symptoms disappeared after discontinuation of ACE inhibitors. Edema of the intestinal mucosa should be included in the differential diagnosis of patients taking ACE inhibitors who complain of abdominal pain.
Patients with a history of angioedema not associated with taking ACE inhibitors may be more at risk of developing angioedema during therapy with ACE inhibitors.
In representatives of the Negroid race, cases of the development of angioedema with the use of ACE inhibitors were noted with a greater frequency compared with representatives of other races.
An increased risk of developing angioedema was observed in patients concomitantly taking ACE inhibitors and drugs such as mTOR inhibitors (temsirolimus, sirolimus, everolimus), type IV dipeptidyl peptidase inhibitors (sitagliptin, saxagliptin, vildagliptin, endagliptin , sacubitril) and tissue plasminogen activators.
Anaphylactic reactions during desensitization
Life-threatening anaphylactoid reactions were noted in two patients during desensitization with hymenoptera venom while taking the ACE inhibitor enalapril. In the same patients, these reactions were avoided by timely suspension of the ACE inhibitor; however, they reappeared after unintentionally resuming an ACE inhibitor. Special care should be taken when desensitizing patients taking ACE inhibitors.
Anaphylactoid reactions during low-density lipoprotein apheresis (LDL apheresis)
Life-threatening anaphylactoid reactions have rarely been observed in patients taking ACE inhibitors during LDL apheresis with dextran sulfate. These reactions can be prevented by temporarily discontinuing the ACE inhibitor prior to each LDL apheresis procedure.
Cough
With the use of ACE inhibitors, including fosinopril, there was an unproductive, persistent cough that disappears after discontinuation of therapy. When a cough occurs in patients taking ACE inhibitors, this therapy should be considered as a possible cause in the differential diagnosis.
Surgery / general anesthesia
ACE inhibitors can enhance the antihypertensive effect of drugs used for general anesthesia. Before surgery (including dentistry), the doctor / anesthetist should be warned about the use of ACE inhibitors. Care should be taken when exercising or in hot weather due to the risk of dehydration and arterial hypotension due to a decrease in the BCC.
Hyperkalemia
There have been cases of an increase in the content of potassium ions in the blood serum of patients taking ACE inhibitors, incl. fosinopril. The risk group in this regard are patients with renal failure, type 1 diabetes mellitus, as well as those taking potassium-sparing diuretics (such as spironolactone, eplerenone, triamterene or amiloride), potassium preparations, potassium-containing dietary supplements or other drugs that increase serum potassium ions blood. If necessary, the simultaneous use of fosinopril and the above-mentioned potassium-containing or potassium-increasing drugs in the blood plasma, care should be taken and the potassium content in the blood serum should be regularly monitored
Double blockade of RAAS
The simultaneous use of drugs of different groups that affect the RAAS (double blockade of the RAAS) is not recommended, since it was associated with an increased incidence of side effects such as arterial hypotension, hyperkalemia, and decreased renal function (including acute renal failure). The simultaneous use of ACE inhibitors with drugs containing aliskiren is contraindicated in patients with diabetes mellitus and / or with moderate or severe renal failure (GFR less than 60 ml / min / 1.73 m2 of body surface area) and is not recommended in other patients. The simultaneous use of ACE inhibitors with ARA II is contraindicated in patients with diabetic nephropathy and is not recommended in other patients.
Hemodialysis using high flow membranes
When performing hemodialysis in patients receiving ACE inhibitors, the use of high-flow polyacrylonitrile dialysis membranes (such as AN69®) should be avoided, as this increases the risk of anaphylactoid reactions. In such cases, it is necessary to use dialysis membranes of a different type or use antihypertensive drugs of other classes.
Ethnic differences
ACE inhibitors are less effective in Negroids than in Caucasians, which may be due to the greater prevalence of low renin activity in Negroids.
Pediatric population
The safety and efficacy of Fosicard H in children has not been established.
Use in elderly patients
Among patients who took a combination of hydrochlorothiazide + fosinopril in clinical trials, 20% were between the ages of 65 and 75 years. There were no differences in safety or efficacy between older and younger patients in general, but higher sensitivity in some older patients cannot be ruled out.
Pregnancy
ACE inhibitor therapy should not be started during pregnancy. Except when treatment with ACE inhibitors is considered necessary, patients planning a pregnancy should be switched to an alternative antihypertensive treatment that has an established safety profile for use during pregnancy. If pregnancy is confirmed, treatment with ACE inhibitors should be stopped immediately, and, if necessary, alternative treatment should be started (see sections "Contraindications" and "Use during pregnancy and breastfeeding").
Fetotoxicity / Neonatal Mortality
When used during pregnancy, ACE inhibitors can cause harm and even death to the developing fetus.

Release form / dosage

Tablets, 12.5 mg + 20 mg.

Packaging

7, 10 or 14 tablets per aluminum foil / PVC / aluminum foil blister.
2, 4 blisters of 7 tablets each, 1, 3 blisters of 10 tablets or 1, 2 blisters of 14 tablets each, together with instructions for use in a cardboard box, on which protective stickers can be applied.

Storage conditions

Store at a temperature not exceeding 25 ° C.
Keep out of the reach of children.
Shelf life - 2 years.
Do not use after the expiration date.

Terms of sell

You can buy Fosicard H without a prescription.