Instructions for Ramimed tablets 10 mg No. 30
Composition
active ingredient: ramipril;
1 tablet contains ramipril 2.5 mg or 5 mg or 10 mg;
excipients: pregelatinized starch (starch 1500); sodium bicarbonate; lactose, monohydrate; croscarmellose sodium; sodium stearyl fumarate; dyes: 2.5 mg tablets - dye RV22960 yellow (lactose, monohydrate; iron oxide yellow (E 172)); 5 mg tablets - dye RV24877 pink (lactose, monohydrate; iron oxide red (E 172); iron oxide yellow (E 172)).
Dosage form
Pills.
Main physicochemical properties:
2.5 mg tablets – pale yellow, capsule-shaped, flat, uncoated tablets with beveled edges, with a score on one side and on both sides and the inscription “R 2”, dimensions approximately 10.0 x 5.0 mm;
5.0 mg tablets – pale pink capsule-shaped, flat, uncoated tablets with beveled edges, with a score on one side and on both sides and the inscription “R 3”, dimensions approximately 8.8 x 4.4 mm;
10 mg tablets – white or almost white, capsule-shaped, flat, uncoated tablets with beveled edges, with a score on one side and on both sides and the inscription “R 4”, dimensions approximately 11.0 x 5.5 mm.
Pharmacotherapeutic group
Angiotensin-converting enzyme (ACE) inhibitors. Monocomponent ACE inhibitors. Ramipril. ATC code C09A A05.
Pharmacological properties
Mechanism of action. Ramiprilat, the active metabolite of the prodrug ramipril, is an inhibitor of the enzyme dipeptidylcarboxypeptidase I (synonyms: angiotensin-converting enzyme; kinase II). In plasma and tissues, this enzyme catalyzes the conversion of angiotensin I to angiotensin II (the active vasoconstrictor) and the cleavage of the active vasodilator bradykinin. The reduction in the formation of angiotensin II and the inhibition of the cleavage of bradykinin lead to vasodilation. Since angiotensin II also stimulates the release of aldosterone, ramiprilat causes a decrease in aldosterone secretion. The response to ACE inhibitor monotherapy was, on average, less pronounced in black (Afro-Caribbean) hypertensive patients (a population characterized by low-renin hypertension) than in patients of other races.
Pharmacodynamics
Antihypertensive properties. Administration of ramipril leads to a significant decrease in peripheral arterial resistance. As a rule, there are no significant changes in renal plasma flow or glomerular filtration rate. Administration of ramipril to patients with arterial hypertension leads to a decrease in blood pressure in both the horizontal and vertical positions of the patient, which is not accompanied by a compensatory increase in heart rate.
In most patients, the antihypertensive effect occurs 1-2 hours after a single oral dose of the drug. The maximum effect after a single oral dose usually occurs after 3-6 hours. The antihypertensive effect after a single dose is usually maintained for 24 hours.
With long-term treatment with ramipril, the maximum antihypertensive effect develops after 3-4 weeks. It has been proven that with long-term therapy, the antihypertensive effect persists for 2 years.
Abrupt discontinuation of ramipril does not cause a rapid and excessive increase in blood pressure (rebound phenomenon).
Heart failure. Ramipril has been shown to be effective in patients with New York Heart Association (NYHA) class II-IV heart failure when used as an adjunct to conventional diuretic therapy and, if necessary, cardiac glycosides. The drug has a beneficial effect on cardiac hemodynamics (reduction of left and right ventricular filling pressures, total peripheral vascular resistance, increase in cardiac output, and improvement in cardiac index). It also reduces neuroendocrine activation.
Pharmacokinetics
Absorption. After oral administration, ramipril is rapidly absorbed from the gastrointestinal tract. Peak plasma concentrations are reached within 1 hour. Based on the amount of substance recovered in the urine, the extent of absorption is at least 56% and is not significantly affected by the presence of food in the gastrointestinal tract. The bioavailability of the active metabolite ramiprilat after oral administration of ramipril at a dose of 2.5 mg and 5 mg is 45%.
Peak plasma concentrations of ramiprilat, the only active metabolite of ramipril, are reached 2-4 hours after administration of ramipril. After the use of usual doses of ramipril once daily, steady-state plasma concentrations of ramiprilat are reached by approximately the 4th day of treatment.
Distribution: The plasma protein binding of ramipril is approximately 73% and that of ramiprilat is approximately 56%.
Elimination. Elimination of metabolites occurs mainly by renal excretion. The decline in plasma concentrations of ramiprilat is multiphasic. Due to the strong saturable binding to ACE and the slow dissociation from the enzyme, ramiprilat has a prolonged terminal elimination phase at very low plasma concentrations.
After repeated doses of ramipril once daily, the effective half-life is 13-17 hours for doses of 5-10 mg and longer for lower doses (1.25-2.5 mg). The difference is due to the saturable capacity of the enzyme to bind ramiprilat.
Neither ramipril nor its metabolite has been detected in breast milk following a single oral dose. However, the effect of repeated doses is unknown.
Patients with renal impairment (see section 4.2). In patients with renal impairment, renal excretion of ramiprilat is reduced and renal clearance of ramiprilat is proportional to creatinine clearance. This results in increased plasma concentrations of ramiprilat, which decrease more slowly than in subjects with normal renal function.
Patients with impaired hepatic function (see section 4.2). In patients with impaired hepatic function, the metabolism of ramipril to ramiprilat was slowed down due to a decrease in the activity of hepatic esterases, and the plasma levels of ramipril were increased in these patients. However, the maximum concentrations of ramiprilat in these patients did not differ from those in subjects with normal hepatic function.
Indication
Treatment of arterial hypertension.
Prevention of cardiovascular disease: reduction of cardiovascular morbidity and mortality in patients with:
- severe cardiovascular disease of atherothrombotic origin (history of ischemic heart disease or stroke or peripheral vascular disease);
- diabetes, who have at least one cardiovascular risk factor (see section "Pharmacological properties").
Treatment of kidney disease:
- initial glomerular diabetic nephropathy, as evidenced by the presence of microalbuminuria;
- severe glomerular diabetic nephropathy, as evidenced by the presence of macroproteinuria, in patients who have at least one cardiovascular risk factor (see section "Pharmacological properties");
- severe glomerular non-diabetic nephropathy, as evidenced by the presence of macroproteinuria ≥ 3 g/day (see section "Pharmacological properties").
Treatment of heart failure accompanied by clinical manifestations.
Secondary prevention after acute myocardial infarction: reduction of mortality during the acute stage of myocardial infarction in patients with clinical signs of heart failure, provided that treatment is started more than 48 hours after the onset of acute myocardial infarction.
Contraindication
Hypersensitivity to the active substance or to any of the excipients included in the preparation, or to other ACE (angiotensin-converting enzyme) inhibitors (see section "Composition").
History of angioedema (hereditary, idiopathic or previously experienced while taking ACE inhibitors or angiotensin II receptor antagonists).
Significant bilateral renal artery stenosis or renal artery stenosis in the presence of a single functioning kidney.
Pregnancy (see section "Use during pregnancy and breastfeeding").
Ramipril should not be used in patients with hypotension or hemodynamically unstable conditions.
Should not be used with aliskiren-containing drugs in patients with diabetes mellitus or moderate or severe renal impairment (GFR < 60 mL/min).
The concomitant use of ACE inhibitors and extracorporeal treatments that result in contact of blood with negatively charged surfaces should be avoided, as such use may lead to severe anaphylactoid reactions. Such extracorporeal treatments include dialysis or hemofiltration using certain membranes with high hydraulic permeability (e.g. polyacrylonitrile) and low-density lipoprotein apheresis using dextran sulfate.
Interaction with other medicinal products and other types of interactions
Contraindicated combinations.
Extracorporeal therapies that result in contact of blood with negatively charged surfaces, such as dialysis or hemofiltration using certain high flux membranes (e.g. polyacrylonitrile membranes) and low density lipoprotein apheresis using dextran sulfate - due to the increased risk of severe anaphylactoid reactions (see section "Contraindications"). If such treatment is necessary, consideration should be given to using a different dialysis membrane or a different class of antihypertensive agent.
The combined use of Ramipril with aliskiren-containing medicinal products is contraindicated in patients with diabetes mellitus or moderately severe renal impairment and is not recommended for other categories of patients (see sections “Contraindications” and “Special warnings and precautions for use”).
Potassium salts, heparin, potassium-sparing diuretics and other active substances that increase plasma potassium levels (including angiotensin II antagonists, trimethoprim, tacrolimus, ciclosporin). Hyperkalaemia may occur, therefore careful monitoring of plasma potassium levels is necessary.
Antihypertensive drugs (e.g. diuretics) and other substances that may lower blood pressure (e.g. nitrates, tricyclic antidepressants, anaesthetics, alcohol, baclofen, alfuzosin, doxazosin, prazosin, tamsulosin, terazosin). An increased risk of hypotension should be expected (see section "Special warnings and precautions for use" for diuretics).
Vasopressor sympathomimetics and other substances (e.g. isoproterenol, dobutamine, dopamine, epinephrine) that may reduce the antihypertensive effect of Ramipril/Amlodipine. Close monitoring of blood pressure is recommended.
Allopurinol, immunosuppressants, corticosteroids, procainamide, cytostatics and other substances that may cause changes in the blood picture.
Increased likelihood of hematological reactions (see section "Special warnings and precautions for use").
Lithium salts: ACE inhibitors may reduce lithium excretion, which may lead to increased lithium toxicity. Lithium levels should be carefully monitored.
Antidiabetic agents, including insulin. Hypoglycemic reactions may occur. Close monitoring of blood glucose levels is recommended.
Non-steroidal anti-inflammatory drugs (NSAIDs) and acetylsalicylic acid. The antihypertensive effect of Ramipril is expected to be reduced. Furthermore, concomitant use of ACE inhibitors and NSAIDs may be associated with an increased risk of worsening of renal function and an increase in blood potassium levels.
Salt. Excessive salt consumption may weaken the hypotensive effect of the drug.
Specific hyposensitization. ACE inhibition increases the likelihood and severity of anaphylactic and anaphylactoid reactions to insect venom. It is believed that this effect may also be observed for other allergens.
Application features
Special categories of patients.
Dual blockade of the renin-angiotensin-aldosterone system (RAAS) with aliskiren-containing medicinal products.
Dual blockade of the renin-angiotensin-aldosterone system through the combined use of Ramipril and aliskiren is not recommended, as there is an increased risk of developing arterial hypotension, hyperkalemia and changes in renal function.
The combined use of Ramipril and aliskiren is contraindicated in patients with diabetes mellitus or renal impairment (GFR 60 ml/min) (see section "Contraindications").
Patients at particular risk of hypotension.
Patients with a strongly activated renin-angiotensin-aldosterone system. Patients with a strongly activated renin-angiotensin-aldosterone system are at risk of a sudden significant fall in blood pressure and deterioration of renal function due to ACE inhibition, particularly when an ACE inhibitor or concomitant diuretic is given for the first time or when the dose is increased for the first time. A strongly activated renin-angiotensin-aldosterone system, requiring medical supervision, including regular monitoring of blood pressure, may be expected, for example, in patients:
- with severe arterial hypertension;
- with decompensated congestive heart failure;
- with hemodynamically significant obstruction to the inflow or outflow of blood from the left ventricle (for example, with aortic or mitral valve stenosis);
- with unilateral renal artery stenosis in the presence of a second functioning kidney;
- in whom there is or may develop a lack of fluid or electrolytes (including those receiving diuretics);
- with liver cirrhosis and/or ascites;
- who are undergoing extensive surgical interventions or during anesthesia with the use of drugs that cause arterial hypotension.
It is generally recommended that dehydration, hypovolemia, or electrolyte depletion be corrected before treatment is initiated (however, in patients with heart failure, such corrective measures should be carefully weighed against the risk of volume overload).
In patients with impaired liver function, the response to treatment with Ramipril may be either enhanced or reduced. In addition, in patients with severe cirrhosis of the liver, accompanied by edema and/or ascites, the activity of the renin-angiotensin system may be significantly increased; therefore, special caution should be exercised when treating these patients.
Transient or persistent heart failure after myocardial infarction.
Patients at risk of cardiac or cerebral ischemia in the event of acute arterial hypotension. Special medical supervision is required in the initial phase of treatment.
Elderly patients.
See section "Method of administration and dosage".
Surgery: If possible, treatment with angiotensin-converting enzyme inhibitors such as ramipril should be discontinued 1 day before surgery.
Renal function should be assessed before and during treatment and the dose adjusted, especially in the first weeks of treatment. Patients with impaired renal function should be monitored particularly closely (see section 4.2). There is a risk of worsening renal function, especially in patients with congestive heart failure or after kidney transplantation.
Angioedema.
Angioedema has been reported in patients treated with ACE inhibitors, including ramipril (see section 4.8). If angioedema develops, Ramipril should be discontinued. Emergency treatment should be initiated immediately. The patient should be kept under medical observation for at least 12-24 hours and may be discharged after complete resolution of symptoms.
Cases of intestinal angioedema have been reported in patients treated with ACE inhibitors, including Ramipril (see section 4.8). These patients presented with abdominal pain (with or without nausea/vomiting).
Anaphylactic reactions during desensitization. When using ACE inhibitors, the likelihood and severity of anaphylactic and anaphylactoid reactions to insect venom and other allergens increases. Before desensitization, Ramipril should be temporarily discontinued.
Hyperkalemia.
Hyperkalemia has been observed in some patients treated with ACE inhibitors, including Ramipril. Patients at risk for hyperkalemia include patients with renal insufficiency, patients over 70 years of age, patients with uncontrolled diabetes mellitus, patients taking potassium salts, potassium-sparing diuretics, or other active substances that increase plasma potassium levels, or patients with conditions such as dehydration, acute cardiac decompensation, or metabolic acidosis. If concomitant use of the above-mentioned drugs is considered appropriate, regular monitoring of plasma potassium levels is recommended (see section 4.5).
Neutropenia/agranulocytosis.
Cases of neutropenia/agranulocytosis, as well as thrombocytopenia and anemia have been observed rarely. Bone marrow suppression has also been reported. Monitoring of the white blood cell count is recommended to detect possible leukopenia. More frequent monitoring is advisable at the beginning of treatment and in patients with impaired renal function, concomitant collagen disease (e.g. systemic lupus erythematosus or scleroderma) or those taking other drugs that can cause changes in the blood picture (see sections “Interaction with other medicinal products and other forms of interaction” and “Adverse reactions”).
Ethnic differences. ACE inhibitors cause angioedema more frequently in black patients than in non-blacks. As with other ACE inhibitors, the antihypertensive effect of ramipril may be less pronounced in black patients than in non-blacks. This may be because black hypertensive patients tend to have low-renin hypertension.
Cough: Cough has been reported with ACE inhibitors. It is characteristic that the cough is non-productive, persistent and resolves after discontinuation of therapy. The possibility of cough due to ACE inhibitors should be considered in the differential diagnosis of cough.
Since the medicinal product contains lactose, patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Use during pregnancy or breastfeeding
Pregnancy. Ramipril is contraindicated during pregnancy (see section 4.3). Therefore, pregnancy should be excluded before starting treatment. Pregnancy should be avoided if treatment with ACE inhibitors is essential.
If the patient plans to become pregnant, treatment with ACE inhibitors should be discontinued, i.e. replaced with another type of treatment.
If the patient becomes pregnant during treatment, Ramipril should be replaced with non-ACE inhibitor therapy as soon as possible.
Breastfeeding: Because no information is available regarding the use of ramipril during breastfeeding (see section 5.1), this drug is not recommended for use in nursing mothers and alternative treatments with better established safety profiles during lactation are preferable, especially while nursing a newborn or preterm infant.
Ability to influence reaction speed when driving vehicles or other mechanisms
This is usually possible at the beginning of treatment or when switching from other drugs to treatment with Ramipril. After taking the first dose or further increasing the dose of the drug, it is advisable not to drive or operate other mechanisms for several hours.
Method of administration and doses
Drug for oral use.
It is recommended to take Ramipril at the same time each day. The drug can be taken before, during, or after meals, as food intake does not affect the bioavailability of the drug. Ramipril tablets should be swallowed whole with water. They should not be chewed or crushed.
Adults.
Patients taking diuretics. At the beginning of treatment with Ramipril, hypotension may occur, the development of which is more likely in patients who are simultaneously receiving diuretics. In such cases, caution is recommended, since these patients may experience a decrease in BCC and / or electrolytes.
It is advisable to discontinue the diuretic 2-3 days before starting treatment with Ramipril, if possible (see section "Special warnings and precautions for use").
In patients with arterial hypertension who cannot discontinue the diuretic, treatment with Ramipril should be initiated at a dose of 1.25 mg. Renal function and blood potassium levels should be closely monitored. Subsequent dosage of Ramipril should be adjusted according to the target blood pressure.
Arterial hypertension.
The dose should be selected individually, depending on the characteristics of the patient's condition (see section "Special instructions for use") and the results of control blood pressure measurements. Ramipril can be used as monotherapy or in combination with other classes of antihypertensive drugs.
Initial dose: Treatment with Ramipril should be initiated gradually, starting with the recommended initial dose of 2.5 mg per day.
In patients with a strongly activated renin-angiotensin-aldosterone system, a significant decrease in blood pressure may occur after the initial dose of the drug. For such patients, the recommended starting dose is 1.25 mg, and their treatment should be initiated under medical supervision (see section "Special instructions").
Dose titration and maintenance dose. The dose may be doubled every 2-4 weeks until the target blood pressure is reached; the maximum dose of Ramipril is 10 mg per day. The drug is usually taken once a day.
Prevention of cardiovascular diseases.
Initial dose. The recommended initial dose of Ramipril is 2.5 mg once daily.
Dose titration and maintenance dose. Depending on individual tolerability, the dose should be increased gradually. It is recommended to double the dose after 1-2 weeks of treatment, and then - after another 2-3 weeks - increase it to the target maintenance dose of 10 mg 1 time per day.
Also see above for dosing information for patients receiving diuretics.
Treatment of kidney disease.
In patients with diabetes and microalbuminuria.
Initial dose. The recommended initial dose of Ramipril is 1.25 mg once daily.
Dose titration and maintenance dose. Depending on individual tolerability of the drug, the dose is increased during further treatment. After 2 weeks of treatment, it is recommended to double the single daily dose to 2.5 mg, and then to 5 mg after another 2 weeks of treatment.
In patients with diabetes and at least one cardiovascular risk factor.
Initial dose. The recommended initial dose of Ramipril is 2.5 mg once daily.
Dose titration and maintenance dose. Depending on individual tolerability of the drug, the dose is increased during further treatment. After 1-2 weeks of treatment, it is recommended to double the daily dose of Ramipril to 5 mg, and then to 10 mg after another 2-3 weeks of treatment. The target daily dose is 10 mg.
In patients with non-diabetic nephropathy, as evidenced by macroproteinuria ≥ 3 g/day.
Initial dose. The recommended initial dose of Ramipril is 1.25 mg once daily.
Dose titration and maintenance dose. Depending on the individual patient's tolerance of the drug, the dose is increased during further treatment. After 2 weeks of treatment, it is recommended to double the single daily dose to 2.5 mg, and then to 5 mg after another 2 weeks of treatment.
Heart failure with clinical manifestations.
Initial dose: For patients stabilized on diuretic therapy, the recommended initial dose is 1.25 mg/day.
Dose titration and maintenance dose. The dose of Ramipril is titrated by doubling it every 1-2 weeks until a maximum daily dose of 10 mg is reached. It is advisable to divide the dose into 2 doses.
Secondary prevention after acute myocardial infarction in the presence of heart failure.
Also see above for dosing information for patients receiving diuretics.
Dose titration and maintenance dose. The daily dose is then increased by doubling it at intervals of 1-3 days until the target maintenance dose of 5 mg twice daily is reached.
Whenever possible, the maintenance daily dose is divided into 2 doses.
If the dose cannot be increased to 2.5 mg twice daily, treatment should be discontinued. Experience in the treatment of patients with severe (NYHA class IV) heart failure immediately after myocardial infarction is still insufficient. If a decision is nevertheless made to treat such patients with this drug, it is recommended to start therapy with a dose of 1.25 mg once daily and any increase should be carried out with extreme caution.
Special categories of patients.
Patients with renal impairment: The daily dose for patients with renal impairment depends on creatinine clearance (see section 5.1):
- if creatinine clearance is ≥ 60 ml/min, there is no need to adjust the initial dose (2.5 mg/day), and the maximum daily dose is 10 mg;
- if creatinine clearance is 30-60 ml/min, there is no need to adjust the initial dose (2.5 mg/day), and the maximum daily dose is 5 mg;
- if creatinine clearance is 10-30 ml/min, the initial daily dose is 1.25 mg/day, and the maximum daily dose is 5 mg;
- patients with arterial hypertension undergoing hemodialysis: ramipril is removed to a small extent during hemodialysis; the initial dose is 1.25 mg, and the maximum daily dose is 5 mg; the drug should be taken a few hours after the hemodialysis session.
Patients with impaired hepatic function (see section "Pharmacological properties"). Treatment with Ramipril in patients with impaired hepatic function should be initiated under close medical supervision, and the maximum daily dose in such cases should be 2.5 mg.
Elderly patients. The initial dose should be lower and subsequent dose titration should be more gradual because of the higher likelihood of adverse effects, especially in very elderly and debilitated patients. In such cases, a lower initial dose of 1.25 mg ramipril should be prescribed.
Children
Ramipril is not recommended for use in children, as there is insufficient data on the efficacy and safety of this drug in such patients.
Overdose
Symptoms associated with overdose of ACE inhibitors may include excessive peripheral vasodilation (with marked hypotension, shock), bradycardia, electrolyte imbalance and renal failure. The patient should be closely monitored and symptomatic and supportive therapy should be administered. The proposed treatment measures include primary detoxification (gastric lavage, administration of adsorbents) and measures aimed at restoring stable hemodynamics, including the administration of alpha-1 adrenoceptor agonists or angiotensin II (angiotensinamide). Ramiprilat, the active metabolite of ramipril, is poorly removed from the systemic circulation by hemodialysis.
Adverse reactions
The safety profile of ramipril includes persistent cough and hypotension-related reactions. Serious adverse reactions include angioedema, hyperkalemia, hepatic or renal impairment, pancreatitis, severe skin reactions, and neutropenia/agranulocytosis.
Cardiac: myocardial ischemia, including angina pectoris or myocardial infarction; tachycardia; arrhythmia; palpitations; peripheral edema.
From the blood and lymphatic system: eosinophilia, decreased white blood cell count (including neutropenia or agranulocytosis), decreased red blood cell count, decreased hemoglobin level, decreased platelet count, bone marrow failure, pancytopenia, hemolytic anemia.
Nervous system: headache, dizziness, vertigo, paresthesia, ageusia, dysgeusia, tremor, balance disorders, cerebral ischemia, including ischemic stroke and transient ischemic attack; impaired psychomotor functions; burning sensation; parosmia.
From the organs of vision: visual disturbances, including blurred vision, conjunctivitis.
From the side of the organs of hearing and labyrinth: hearing impairment, tinnitus.
Respiratory, thoracic and mediastinal disorders: non-productive irritating cough, bronchitis, sinusitis, dyspnea, bronchospasm, including exacerbation of asthma; nasal congestion.
Gastrointestinal: gastrointestinal inflammation, indigestion, abdominal discomfort, dyspepsia, diarrhea, nausea, vomiting, pancreatitis (in isolated cases, fatal outcomes have been reported with the use of ACE inhibitors), increased pancreatic enzymes, angioedema of the small intestine, upper abdominal pain, including gastritis, constipation, dry mouth, glossitis, aphthous stomatitis.
Skin and subcutaneous tissue disorders: rash, particularly maculopapular, angioedema; in very exceptional cases, airway obstruction due to angioedema, which may be fatal; pruritus, hyperhidrosis, exfoliative dermatitis, urticaria, onycholysis, photosensitivity reaction, toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, pemphigus, exacerbation of psoriasis, psoriatic dermatitis, pemphigoid or lichenoid exanthema or enanthema, alopecia.
Musculoskeletal and connective tissue disorders: muscle spasms, myalgia, arthralgia.
On the part of the endocrine system: syndrome of inappropriate antidiuretic hormone secretion (SIADH).
Metabolic and nutritional disorders: increased blood potassium levels, anorexia, decreased appetite, decreased blood sodium levels.
Vascular: hypotension, orthostatic hypotension, syncope, flushing, vascular stenosis, hypoperfusion, vasculitis, Raynaud's phenomenon.
General disorders: chest pain, fatigue, pyrexia, asthenia.
On the part of the immune system: anaphylactic and anaphylactoid reactions, increased levels of antinuclear antibodies.
On the part of the hepatobiliary system: increased levels of liver enzymes and/or bilirubin conjugates, cholestatic jaundice, liver cell damage, acute liver failure, cholestatic or cytolytic hepatitis (in very exceptional cases - with a fatal outcome).
Reproductive system and breast disorders: transient erectile impotence, decreased libido, gynecomastia.
On the part of the psyche: decreased mood, anxiety, nervousness, restlessness, sleep disturbances, including drowsiness, a state of confusion, impaired attention.
Expiration date
2 years.
Storage conditions
Store at a temperature not exceeding 25 °C in the original packaging, out of the reach of children.
Incompatibility
No data.
Packaging
10 tablets in a blister. 3 blisters in a cardboard box.
Vacation category
According to the recipe.
Producer
Actavis Ltd.
Location of the manufacturer and its business address
BLB 016, Bulebel Industrial Estate, Zejtun ZTN3000, Malta/BLB 016, Bulebel Industrial Estate, Zejtun ZTN3000, Malta.
