Instructions for Zocardis 7.5 mg film-coated tablets 7.5 mg No. 28
Composition
active ingredient: 1 film-coated tablet contains 7.5 mg of zofenopril calcium, which is equivalent to 7.2 mg of zofenopril;
excipients:
core: microcrystalline cellulose, lactose monohydrate, croscarmellose sodium, magnesium stearate, colloidal anhydrous silicon dioxide;
film coating: hypromellose, titanium dioxide (E 171), polyethylene glycol 400, polyethylene glycol 6000.
Dosage form
Film-coated tablets.
Main physicochemical properties: white, round, biconvex tablets, film-coated.
Pharmacotherapeutic group
Angiotensin-converting enzyme (ACE) inhibitors, monocomponent.
ATX code C09A A15.
Pharmacological properties
Pharmacodynamics.
The mechanism of action of the drug Zocardis® in hypertension and acute myocardial infarction is mainly due to inhibition of the renin-angiotensin-aldosterone system in the blood plasma. Inhibition of ACE (Ki 0.4 nM in rabbit lungs for zofenoprilat arginine salt) leads to a decrease in the level of angiotensin II in the blood plasma, as a result of which the vasoconstrictor activity and secretion of aldosterone are reduced. At the same time, with a slight decrease in the level of the latter, a slight increase in the concentration of potassium in the blood serum is possible, which is accompanied by loss of sodium and fluid. As a result of inhibition of the effect of angiotensin II on renin secretion, renin activity in the blood plasma increases. Plasma ACE activity decreases by 53.4% and 74.4% 24 hours after administration of a single oral dose of 30 mg and 60 mg of zofenopril calcium, respectively.
Inhibition of ACE leads to increased activity of the circulating and local kallikrein-kinin system, which affects peripheral vasodilation through activation of the prostaglandin system. This mechanism is probably involved in the hypotensive effect of zofenopril calcium and is responsible for certain side effects. In patients with arterial hypertension, the use of Zocardis® leads to a similar decrease in blood pressure in the supine and standing positions without a compensatory increase in heart rate. After the use of Zocardis®, the average systemic vascular resistance tends to decrease. For some patients, achieving optimal blood pressure reduction may require several weeks of therapy. The antihypertensive effect is maintained with prolonged therapy. Abrupt discontinuation of therapy does not result in a rapid increase in blood pressure. To date, there are no data on the effect of Zocardis® on morbidity and mortality in patients with arterial hypertension. Although the study showed an antihypertensive effect in patients of all races, the average response to monotherapy with an ACE inhibitor in blacks (usually in a hypertensive population with low-renin levels) is lower than in other patients. This difference disappears when a diuretic is added. The clinical effect of early use of Zocardis® after myocardial infarction may be due to many factors, such as a decrease in plasma angiotensin II levels (thereby limiting the process of ventricular remodeling, which can negatively affect the prognosis of survival of the patient with infarction) and an increase in plasma/tissue concentrations of vasodilator substances (prostaglandin-kinin system).
A randomized, placebo-controlled clinical trial of zofenopril was conducted in 1556 patients with a previous myocardial infarction who were not receiving thrombolytic therapy. Treatment was started within 24 hours and continued for 6 weeks. In the group of patients treated with zofenopril, the rates of the main combined endpoints (severe heart failure and/or fatal outcome within 6 weeks) were reduced: zofenopril - 7.1%, placebo - 10.6%. After one year, the survival rate was better in the group using the drug Zocardis®.
Other information
Two large randomized controlled trials (ONTARGET (current telmisartan as monotherapy and in combination with ramipril, Global Endpoint Trial) and VA NEPHRON-D (diabetic nephropathy)) studied the use of a combination of ACE inhibitors with angiotensin II receptor inhibitors.
ONTARGET - a study conducted in patients with cardiovascular and cerebrovascular diseases or type 2 diabetes mellitus, accompanied by signs of target organ damage. VA NEPHRON-D - a study conducted in patients with type 2 diabetes mellitus and diabetic nephropathy. These studies did not show a significant positive effect on renal function and/or cardiovascular outcomes and mortality, while an increased risk of hyperkalemia, acute kidney injury and/or hypotension was observed compared with monotherapy. Given the similar pharmacodynamic properties, these results also apply to other ACE inhibitors and angiotensin II receptor blockers.
ALTITUDE (Aliskiren in Type 2 Diabetes with Cardiovascular and Renal Endpoints Trial) is a study of the benefit of adding aliskiren to standard therapy with an ACE inhibitor or angiotensin II receptor blocker in patients with type 2 diabetes and chronic kidney disease, cardiovascular disease, or both. The study was stopped early due to an increased risk of adverse outcomes. The number of deaths from cardiovascular disease and stroke was higher in the aliskiren group than in the placebo group, and serious adverse reactions (hyperkalemia, hypotension, and renal dysfunction) were reported more frequently in the aliskiren group than in the placebo group.
Pharmacokinetics.
Zofenopril calcium is a prodrug because the active inhibitor is the sulfhydryl moiety of zofenoprilat, which is formed upon hydrolysis by thioesters.
Absorption
Zofenopril calcium is rapidly and completely absorbed after oral administration and is almost completely converted to zofenoprilat, the peak blood level of which is reached 1.5 hours after oral administration of Zocardis®. Single dose kinetics are linear in the dose range of 10–80 mg zofenopril calcium, and after administration of 15–60 mg zofenopril calcium for 3 weeks, no accumulation occurs. Food in the gastrointestinal tract reduces the rate of absorption of the drug, but not its extent, and the AUC of zofenoprilat is almost the same after administration with food or on an empty stomach.
Distribution
After administration of radiolabeled zofenopril calcium, approximately 88% of the circulating radioactivity is bound to plasma proteins ex vivo, and the volume of distribution at steady state is 96 l.
Biotransformation
Following administration of radiolabeled zofenopril calcium in human urine, 8 metabolites have been identified, accounting for 76% of the urinary radioactivity. The major metabolite is zofenoprilat (22%), which is then metabolized by several pathways including glucuronide conjugation (17%), cyclization and glucuronide conjugation (13%), conjugation with cysteine (9%) and S-methylation of the thiol group (8%). Following oral administration of zofenopril calcium, the elimination half-life of zofenoprilat is 5.5 hours and the total body clearance is
1300 ml/min.
Breeding
Radiolabeled zofenoprilat after intravenous administration is excreted in urine (76%) and feces (16%), while after oral administration of radiolabeled zofenopril calcium, 69% and 26% of the radioactivity are excreted in urine and feces, respectively, indicating a dual elimination pathway (kidney and liver).
Pharmacokinetics in specific patient groups
Elderly patients
For elderly patients, there is no need for dose adjustment if renal function is normal.
Kidney dysfunction
Based on a comparison of the main pharmacokinetic parameters of zofenopril after oral administration of radiolabeled zofenopril calcium, it was found that in patients with renal impairment (creatinine clearance > 45 and < 90 ml/min) zofenopril is eliminated at the same rate as in patients with normal renal function (creatinine clearance > 90 ml/min).
In patients with moderate to severe renal impairment (7–44 mL/min), the elimination rate is reduced by 50% of normal. This indicates that half the usual starting dose of Zocardis® should be used in such patients.
In patients with end-stage renal disease undergoing hemodialysis and peritoneal dialysis, the elimination rate is reduced to 25% of normal. This indicates that a quarter of the usual starting dose of Zocardis® should be used in such patients.
Liver dysfunction
In patients with mild to moderate hepatic impairment given single doses of radiolabelled zofenopril calcium, the Cmax and Tmax of zofenoprilat were similar to those in patients without hepatic impairment. However, the AUC values in cirrhotic patients were almost twice those in patients with normal hepatic function. This suggests that patients with mild to moderate hepatic impairment should be given half the usual starting dose of Zocardis® used in patients with normal hepatic function.
There are no data on the pharmacokinetics of zofenopril and zofenoprilat in patients with severe hepatic impairment, therefore zofenopril is contraindicated in such patients.
Indication
Arterial hypertension
Treatment of mild to moderate essential hypertension.
Acute myocardial infarction
Treatment of acute myocardial infarction (first 24 hours) with signs and symptoms (or without them) of heart failure with stable hemodynamics, provided that thrombolytic therapy has not been performed.
Contraindication
Hypersensitivity to zofenopril calcium or to any other ACE inhibitor, or to any of the excipients included in the formulation.
Concomitant use with sacubitril/valsartan: Treatment with Zocardis® should be initiated no earlier than 36 hours after the last dose of sacubitril/valsartan (see sections “Special warnings and precautions for use” and “Interaction with other medicinal products and other forms of interaction”).
Hereditary or idiopathic angioedema.
Severe liver dysfunction.
Bilateral renal artery stenosis or arterial stenosis of a single functioning kidney.
Pregnancy or planning to become pregnant (see section "Use during pregnancy or breastfeeding").
The drug is contraindicated in women of reproductive age who are not using effective contraception.
The simultaneous use of Zocardis® with drugs containing aliskiren is contraindicated in patients with diabetes mellitus or renal insufficiency (GFR < 60 ml/min/1.73 m2).
Interaction with other medicinal products and other types of interactions
Medicines that increase the risk of developing angioedema
The concomitant use of ACE inhibitors and sacubitril/valsartan is contraindicated due to an increased risk of angioedema (see sections “Contraindications” and “Special warnings and precautions for use”).
Concomitant use of ACE inhibitors with racecadotril, mTOR inhibitors (e.g. sirolimus, everolimus, temsirolimus) and vildagliptin may lead to an increased risk of angioedema (see section 4.4).
Concomitant use with the following medicines is not recommended.
Potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium, and other drugs that increase potassium levels
Although serum potassium levels usually remain within normal limits, hyperkalaemia may occur in some patients taking zofenopril. Potassium-sparing diuretics (e.g. spironolactone, triamterene or amiloride), potassium supplements or potassium-containing salt substitutes may lead to significant increases in serum potassium. Caution should also be exercised when zofenopril is administered concomitantly with other agents that increase serum potassium levels, such as trimethoprim and co-trimoxazole (trimethoprim/sulfamethoxazole), as trimethoprim is known to act as a potassium-sparing diuretic, similar to amiloride. Therefore, the combination of zofenopril with the above-mentioned medicinal products is not recommended. If such a combination proves necessary, it should be used with caution and with frequent monitoring of serum potassium.
ACE inhibitors, angiotensin II receptor blockers, or aliskiren
Clinical studies have shown that dual blockade of the RAAS through the simultaneous use of ACE inhibitors, angiotensin II receptor blockers or aliskiren is associated with an increased risk of adverse reactions such as hypotension, hyperkalemia and decreased renal function (including acute renal failure) compared with the use of a single RAAS-active drug (see sections "Contraindications", "Special instructions for use", "Pharmacodynamics").
Concomitant use with the following medicines requires special caution.
Diuretics (thiazide or loop diuretics). Previous use of high doses of diuretics may lead to dehydration and a risk of hypotension at the beginning of treatment with zofenopril. The likelihood of a hypotensive effect can be reduced by discontinuing the diuretic, increasing the patient's fluid and salt intake, or starting therapy with low doses of zofenopril.
Lithium: Reversible increases in serum lithium concentrations and toxicity have been reported with concomitant use of ACE inhibitors. Concomitant use of thiazide diuretics with lithium may increase the risk of lithium toxicity, which is exacerbated by concomitant use of ACE inhibitors. Therefore, zofenopril is not recommended for use with lithium and, if necessary, serum lithium levels should be monitored closely.
Gold: There have been reports that patients taking ACE inhibitors and receiving injectable gold preparations (e.g., sodium aurothiomalate) are more likely to develop nitrate-like reactions (symptoms of vasodilation, including flushing, nausea, dizziness, hypotension), which can be quite severe.
Anesthetic drugs: ACE inhibitors may enhance the hypotensive effect of anesthetic drugs.
Narcotics/tricyclic antidepressants/antipsychotics/barbiturates: Orthostatic hypotension may occur.
Other antihypertensive agents (beta-blockers, alpha-blockers, calcium antagonists). Additive hypotensive effect or potentiation of the drug action is possible. Nitroglycerin and other nitrates and vasodilators should be used with caution.
Cimetidine: Increased risk of developing arterial hypotension.
Cyclosporine: Hyperkalemia may occur when ACE inhibitors are used concomitantly with cyclosporine. Monitoring of serum potassium is recommended.
Allopurinol, cytostatics, immunosuppressants, systemic corticosteroids and procainamide. Concomitant use with ACE inhibitors increases the risk of hypersensitivity reactions. Concomitant use with ACE inhibitors may increase the risk of leukopenia.
Antidiabetic agents: Rarely, ACE inhibitors may potentiate the hypoglycaemic effect of insulin and oral antidiabetic agents, such as sulphonylureas, in diabetic patients. Therefore, a reduction in the dose of the antidiabetic agent may be necessary when co-administered with ACE inhibitors.
Hemodialysis using high-flux dialysis membranes. Concomitant use with ACE inhibitors increases the risk of anaphylactoid reactions.
This should be taken into account when used simultaneously.
Non-steroidal anti-inflammatory drugs (including acetylsalicylic acid at a dose of ≥ 3 g/day). The antihypertensive effect of ACE inhibitors may be reduced. In addition, NSAIDs and ACE inhibitors further increase serum potassium levels, while renal function may deteriorate. These effects are reversible and occur more often in patients with reduced renal function. Acute renal failure may occur rarely, especially in patients with impaired renal function, in particular in elderly or dehydrated patients.
Antacids reduce the bioavailability of ACE inhibitors.
Sympathomimetics may reduce the antihypertensive effect of ACE inhibitors. Such patients should be carefully monitored to ensure that the desired effect is achieved.
Food: The rate, but not the extent, of absorption of zofenopril calcium may be reduced.
Additional information: No direct clinical data are available on the interaction of zofenopril with other drugs metabolized by CYP enzymes. However, in vitro metabolism studies of zofenopril demonstrate no potential for interaction with drugs metabolized by CYP enzymes.
Application features
Hypotension
As with other ACE inhibitors, Zocardis® may cause a significant decrease in blood pressure, especially after the first dose, although symptomatic hypotension is rare in patients with uncomplicated hypertension. It is more likely to occur in patients who are volume-depleted by diuretic therapy, dietary salt restriction, diarrhea, or vomiting, or in those with severe renin-dependent hypertension.
Symptomatic hypotension has been reported in patients with heart failure, whether associated with or without renal insufficiency. It is more likely in patients with more severe heart failure, such as those receiving high doses of loop diuretics, hyponatremia, or impaired renal function. Treatment of patients at increased risk of symptomatic hypotension should be initiated under close medical supervision, preferably in a clinic, with low doses and careful titration.
If possible, diuretic treatment should be temporarily discontinued at the beginning of Zocardis® therapy.
The same approach also applies to patients with angina or cerebrovascular disease, in whom excessive hypotension could lead to myocardial infarction or cerebrovascular attack.
If hypotension develops, the patient should be placed in the supine position. Electrolyte volume replacement by intravenous saline may be necessary. The occurrence of hypotension after the first dose does not preclude subsequent careful titration of the drug dose after effective control.
Some heart failure patients with normal or low blood pressure may experience an additional decrease in systemic blood pressure when using Zocardis®. This is an expected effect and is not usually a reason for discontinuation of treatment. If hypotension becomes symptomatic, a dose reduction or discontinuation of Zocardis® may be necessary.
Hypotension in acute myocardial infarction
Treatment with Zocardis® should not be initiated in patients with acute myocardial infarction if there is a risk of additional serious haemodynamic depression after treatment with vasodilators. This applies to patients with systolic blood pressure < 100 mm Hg or in the event of cardiogenic shock. Treatment of patients with acute myocardial infarction with Zocardis® may lead to severe hypotension. In the event of prolonged hypotension (systolic blood pressure
< 90 mm Hg for more than 1 hour) Zocardis® should be discontinued. In patients with severe heart failure after acute myocardial infarction, Zocardis® should only be used if the patient is hemodynamically stable.
Patients with acute myocardial infarction with liver failure
The efficacy and safety of Zocardis® in patients with hepatic insufficiency in the event of a myocardial infarction have not been established. Therefore, Zocardis® should not be used in these patient groups.
Elderly patients
Zocardis® should be used with caution in elderly (aged 75 years and over) patients with myocardial infarction.
There is an increased risk of severe hypotension and renal failure when ACE inhibitors are used in patients with renovascular hypertension and pre-existing bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney. Diuretic treatment may be an additional factor. In patients with unilateral renal artery stenosis, loss of renal function may occur even with small changes in serum creatinine. If treatment with Zocardis® is considered absolutely necessary, it should be initiated in hospital under close medical supervision, with low doses and with careful dose titration. At the beginning of Zocardis® therapy, diuretic treatment should be temporarily discontinued and renal function should be monitored during the first few weeks of therapy.
Patients with renal insufficiency
Zocardis® should be used with caution in patients with renal insufficiency, as they require a lower dosage. Careful monitoring of renal function is important during therapy. Cases of renal insufficiency have been reported with ACE inhibitors, occurring predominantly in patients with severe heart failure or pre-existing renal disease, including renal artery stenosis. In some patients with pre-existing minor renal disease, increases in blood urea and creatinine have occurred, particularly when used concomitantly with a diuretic. A reduction in the dose of the ACE inhibitor and/or discontinuation of the diuretic may be necessary. Monitoring of renal function is recommended during the first few weeks of therapy.
The efficacy and safety of Zocardis® in patients with renal impairment in the event of myocardial infarction have not been established. Therefore, Zocardis® should not be used in patients with renal impairment (serum creatinine ≥ 2.1 mg/dl and proteinuria ≥ 500 mg/day) and myocardial infarction.
Patients on dialysis
In patients on dialysis with high-flux polyacrylonitrile membranes (e.g.,
AN 69) receiving ACE inhibitors, anaphylactic reactions such as facial edema, flushing, hypotension, and dyspnea may occur during the first minutes of hemodialysis. It is recommended to use an alternative membrane or another antihypertensive drug.
The efficacy and safety of Zocardis® in patients with myocardial infarction undergoing hemodialysis have not been established. Therefore, it should not be used in such patients.
Patients undergoing LDL apheresis
Patients receiving ACE inhibitors and undergoing LDL apheresis with dextran sulfate may experience anaphylactic reactions similar to those seen with dialysis with high-flux polyacrylonitrile membranes (see above). In such patients, the use of a different class of antihypertensive drug is recommended.
Anaphylactic reactions during desensitization or after insect bites
Life-threatening anaphylactic reactions have been reported rarely in patients receiving desensitization therapy (e.g., hymenoptera venom) or insect stings. These reactions have been avoided by temporarily withholding ACE inhibitors, but have recurred when the drug is reintroduced in these patients. Therefore, special caution should be exercised in patients receiving ACE inhibitors during these desensitization procedures.
Kidney transplantation
There is no experience with the use of Zocardis® in patients with a recent kidney transplant.
Primary aldosteronism
Patients with primary aldosteronism will generally not respond to antihypertensive drugs that act by inhibiting the renin-angiotensin system. Therefore, the use of this drug is not recommended.
Hypersensitivity/angioedema
Patients may experience angioedema of the face, extremities, lips, mucous membranes, tongue, glottis and/or larynx, most often occurring within the first weeks of treatment with ACE inhibitors. However, severe angioedema may occasionally develop after prolonged treatment with angiotensin-converting enzyme inhibitors. In such cases, ACE inhibitors should be discontinued promptly and a different class of drug should be substituted for continued therapy.
Angioedema of the tongue, glottis or larynx can be fatal. Emergency treatment should be given, which may include subcutaneous injection of epinephrine 1:1000 (0.3 to 0.5 ml) or slow intravenous injection of epinephrine 1 mg/ml (diluted according to instructions) with close monitoring of ECG and blood pressure. The patient should be hospitalized and monitored for at least 12–24 hours and not discharged until symptoms have resolved.
Even in cases where only tongue swelling occurs without respiratory distress syndrome, monitoring of the patient may be necessary, as treatment with antihistamines and corticosteroids may not be sufficient.
ACE inhibitors cause a higher rate of angioedema in patients of the Negroid race than in representatives of other races.
Concomitant use of ACE inhibitors and sacubitril/valsartan is contraindicated due to an increased risk of angioedema. Sacubitril/valsartan treatment should be initiated no earlier than 36 hours after the last dose of Zocardis®. Zocardis® treatment should be initiated no earlier than 36 hours after the last dose of sacubitril/valsartan (see sections “Contraindications” and “Interaction with other medicinal products and other types of interactions”).
Concomitant use of ACE inhibitors with racecadotril, mTOR inhibitors (e.g. sirolimus, everolimus, temsirolimus) and vildagliptin may increase the risk of angioedema (e.g. swelling of the airways or tongue with or without respiratory distress) (see section 4.5). Particular caution should be exercised when initiating therapy with racecadotril, mTOR inhibitors (e.g. sirolimus, everolimus, temsirolimus) and vildagliptin in patients already taking ACE inhibitors.
Cough
During treatment with Zocardis®, a dry and unproductive cough may occur, which disappears after discontinuation of Zocardis®. Cough caused by the use of ACE inhibitors should be considered in the differential diagnosis of cough.
Liver failure
Rarely, the use of ACE inhibitors has been associated with a syndrome that begins with cholestatic jaundice and progresses to fulminant hepatic necrosis, sometimes fatal. The mechanism of this syndrome is not known. Patients taking ACE inhibitors who develop jaundice or significant elevations of liver enzymes should discontinue ACE inhibitors and receive appropriate medical attention.
Serum potassium
ACE inhibitors may cause hyperkalaemia because they inhibit the release of aldosterone. In patients with normal renal function, the effect is usually negligible. However, in patients with impaired renal function and/or in patients taking potassium supplements (including salt substitutes), potassium-sparing diuretics, heparin, trimethoprim or co-trimoxazole, also known as trimethoprim/sulfamethoxazole, and especially aldosterone antagonists or angiotensin receptor blockers, hyperkalaemia may occur. Potassium-sparing diuretics and angiotensin receptor blockers should be used with caution in patients taking ACE inhibitors, and serum potassium and renal function should be monitored (see section 4.5).
Dual blockade of the renin-angiotensin-aldosterone system (RAAS)
There is evidence that the concomitant use of ACE inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of hypotension, hyperkalaemia and decreased renal function (including acute renal failure). Therefore, dual blockade of the RAAS through the combined use of ACE inhibitors, angiotensin II receptor blockers or aliskiren is not recommended (see sections 4.5 and 5.1).
If double blockade is considered absolutely necessary, it should only be performed under specialist supervision and with frequent, careful monitoring of renal function, electrolytes and blood pressure.
ACE inhibitors and angiotensin II receptor blockers should not be used concomitantly in patients with diabetic nephropathy.
Surgery/anesthesia
ACE inhibitors may cause hypotension and even shock in patients undergoing abdominal surgery or during anesthesia because they may block the formation of angiotensin II, leading to compensatory renin release. If ACE inhibitors cannot be discontinued, intravascular and plasma volume should be carefully monitored.
Aortic, mitral stenosis, or hypertrophic cardiomyopathy. ACE inhibitors should be used with caution in patients with mitral stenosis and obstruction in the outflow of blood from the left ventricle.
Neutropenia/agranulocytosis
When zofenopril is used in such patients, it is recommended that a white blood cell count and differential be performed prior to therapy, every 2 weeks for the first 3 months of zofenopril therapy, and periodically thereafter. During treatment, patients should be advised to report any signs of infection (such as sore throat, fever) and a white blood cell count should be performed. If neutropenia (neutrophil count less than 1000/mm3) is diagnosed or suspected, zofenopril and other concomitant medications should be discontinued.
This syndrome is reversible after discontinuation of the ACE inhibitor.
Psoriasis
ACE inhibitors should be used with caution in patients with psoriasis.
Proteinuria
Proteinuria may occur, in particular, in patients with pre-existing renal impairment or who are receiving relatively high doses of ACE inhibitors. In patients with a history of renal disease, urine protein should be measured (first morning urine dipstick) before treatment and periodically thereafter.
Patients with diabetes
In patients with diabetes mellitus already taking antidiabetic drugs or insulin, blood sugar levels should be closely monitored during the first month of treatment with an ACE inhibitor (see section “Interaction with other medicinal products and other types of interactions”).
Lithium
The combination of lithium and Zocardis® is generally not recommended (see section “Interaction with other medicinal products and other types of interactions”).
Ethnic differences
Like other ACE inhibitors, zofenopril may be less effective in lowering blood pressure in black patients than in non-black patients.
The risk of angioedema due to ACE inhibitors is higher in patients of the Negroid race.
Pregnancy
Zocardis® is contraindicated in pregnant women and women planning to become pregnant. If pregnancy is confirmed during treatment with Zocardis®, its use should be discontinued immediately and replaced with another drug approved for use in pregnant women.
Other
This medicinal product contains lactose and should not be used in patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.
Use during pregnancy or breastfeeding
Pregnancy
ACE inhibitors are contraindicated in pregnant women and women planning to become pregnant (see section "Contraindications"). Epidemiological data on the risk of teratogenesis due to the use of ACE inhibitors in the first trimester of pregnancy are not conclusive, but a slight increase in risk cannot be excluded. If long-term therapy with ACE inhibitors is necessary, alternative treatment with antihypertensive drugs with proven safety is indicated for women planning pregnancy. If pregnancy is confirmed during treatment with this drug, its use should be discontinued immediately and replaced with another drug approved for use in pregnant women. In the case of the use of ACE inhibitors in the second and third trimesters of pregnancy, the appearance of fetotoxic effects (deterioration of renal function, oligohydramnios, delayed ossification of the skull) and in newborns - renal failure, arterial hypotension and hyperkalemia. In case of fetotoxic effects during ACE inhibitor therapy in the II and III trimesters of pregnancy, patients are shown ultrasound examination to check renal function and the condition of the skull bones. The condition of children whose mothers used ACE inhibitors during pregnancy should be carefully monitored for arterial hypotension.
Breast-feeding
Because no information is available regarding the use of zofenopril during breast-feeding, its use is not recommended in breast-feeding women. Alternative treatments are preferable, especially while nursing a newborn or preterm infant.
