Ramazid N, tablets 5 mg+12, 5 mg 30 pcs

Hypertension (high blood pressure), OedemaArterial hypertension (patients who are indicated for combination therapy).

Active ingredient

Hydrochlorothiazide, Ramipril

How to take, the dosage

The drug is not intended for initial therapy of arterial hypertension, since in patients who have not previously received treatment with hypotensive drugs and who are immediately started on treatment with ramipril and a diuretic, an excessive decrease in BP may occur.

Interaction

Contraindicated combinations
– Extracorporeal treatments leading to blood contact with negatively charged surfaces, such as hemodialysis or hemofiltration with certain high-strength membranes (polyacrylonitrile membranes) and low-density lipoprotein apheresis with dextrin sulfate.
Risk of severe anaphylactoid reactions (see section “Contraindications”, “Special indications”).
– Simultaneous use of Ramazid N (12.5/5 mg) and drugs containing aliskiren
Simultaneous use of Ramazid N (12.5/5 mg) and drugs containing aliskiren in patients with diabetes or moderate to severe renal impairment and creatinine clearance less than 60 ml/min is contraindicated and not recommended in other patients (see “Contraindications. Section “Contraindications”, “With caution” “Special indications”).
– Concomitant use of Ramazid N (12.5/5 mg) and angiotensin II receptor antagonists
Concomitant use of Ramazid N (12.5/5 mg) and angiotensin II receptor antagonists is contraindicated in patients with diabetic nephropathy and is not recommended in other patients (see sect. See Contraindications, Caution, and Particular Indications).

Unrecommended combinations
– With potassium salts, potassium-saving diuretics (e.g., spironolactone, epleron [spironolactone derivative], amiloride, triamterene), other drugs that can increase serum potassium levels (including angiotensin II receptor antagonists, tacrolimus, cyclosporine, trimethoprim, sulfamethoxazole, a component of co-trimoxazole [a combined antibacterial agent containing trimethoprim and sulfamethoxazole]).
Increase in serum potassium is possible, sometimes significantly pronounced (with concomitant use careful monitoring of serum potassium is required).

Combinations in which caution should be exercised
– With hypotensive drugs and other drugs with antihypertensive effect (nitrites, tricyclic antidepressants)
Potentiation of antihypertensive effect is possible.
With agents for general anesthesia, barbiturates, ethanol
Orthostatic hypotension may develop. Ramipril may potentiate the vasodilator effect of ethanol.
– With diuretics
An excessive decrease in BP at the beginning of treatment is possible (regarding concomitant use with diuretics, see section “Contraindications”, “With caution” “Special notes”).
– With vasopressor sympathomimetics (epinephrine (adrenaline), isoproterenol, dobutamine, dopamine)
Decrease of antihypertensive effect of Ramazid N (12.5/5 mg). It is recommended to monitor BP carefully. In addition, the vasopressor effect of sympathomimetics may be weakened by hydrochlorothiazide.
– With allopurinol, immunosuppressive drugs, corticosteroids (glucocorticoids and mineralcorticoids), procainamide, cytostatics and other drugs that may alter the peripheral blood
The possibility of blood disorders increases (see section “Side effects”, “Precautions”).
– With lithium salts
Reduction of lithium excretion is possible, leading to increased serum concentrations of lithium and increasing its toxicity. Therefore, serum concentrations of lithium should be monitored regularly.
– With hypoglycemic agents (e.g., insulin, hypoglycemic agents for oral administration (sulfonylurea derivatives).
ACE inhibitors may decrease insulin resistance. In some cases, in patients receiving hypoglycemic agents, such decrease in insulin resistance may lead to the development of hypoglycemia. This effect may develop after several days or months of treatment. Hydrochlorothiazide may weaken the effect of hypoglycemic agents. Therefore, at the initial stage of concomitant use of hypoglycemic agents and Ramazide N (12.5/ 5 mg), especially careful monitoring of blood glucose concentration is required.
– With vildagliptin, other glyptins and estramustine
Increased incidence of angioedema.
– With mTOR inhibitors (mammalian Target of Rapamycin in mammalian cells), such as temsirolimus

Combinations to consider
– With nonsteroidal anti-inflammatory drugs (indomethacin, acetylsalicylic acid (over 3 g/day).
The action of the drug Ramazid N (12.5/5 mg) may be impaired, the risk of renal dysfunction and the increase of serum potassium ions may increase.
Strict monitoring of serum creatinine and potassium concentrations is recommended.
– With heparin
Possible increase in serum potassium.
– With corticosteroids (glucocorticoids and mineralcorticoids), carbenoxolone, preparations containing licorice root, laxatives (when taken for a long time) and other potassium-regulating agents
There is an increased risk of hypokalemia.
– With cardiac glycosides, drugs that may prolong the QT interval, antiarrhythmic agents
Potential development of hypokalemia or hypomagnesemia (due to the content of hydrochlorothiazide in the drug) that may lead to potentiation of proarrhythmogenic effect of these drugs or to decrease the antiarrhythmic effect of antiarrhythmic agents.
– With methyldopa
Hemolysis is possible
– With calcium salts and drugs that increase the calcium content in the blood plasma
With hydrochlorothiazide simultaneous use may increase the calcium content in the blood serum.
– With vitamin D
In concomitant use with hydrochlorothiazide increased serum calcium content is possible (due to delayed renal excretion of calcium), requires careful monitoring of serum calcium.
– With carbamazepine
Risk of hyponatremia due to the potentiating effect of hydrochlorothiazide.
– With iodine-containing contrast agents
In the case of dehydration caused by diuretics, including hydrochlorothiazide, there is an increased risk of acute renal dysfunction, especially when administering high doses of contrast agent.
– With penicillin
Hydrochlorothiazide is excreted by the distal renal tubules and therefore reduces the excretion of penicillin.
– With quinidine
Hydrochlorothiazide reduces the excretion of quinidine.
– With orally administered ion exchange resins such as colestipol and colestirami
Absorption of hydrochlorothiazide is reduced.
– With non-depolarizing myorelaxants
Possible enhancement and prolongation of the myorelaxant effect.
– With table salt.
If there is a large quantity of table salt in food, the antihypertensive effect of Ramazid H (12.5/5 mg) may decrease.
– With desensitization therapy
The likelihood and severity of anaphylactic reactions to insect venom is increased with ACE inhibition. It is assumed that similar reactions are possible to other allergens.
– With warfarin, acenocoumarol
When used concomitantly with ramipril, no effect on the anticoagulant effect of these drugs was observed.

Influence on the results of laboratory tests
– Assessment of parathyroid function
Hydrochlorothiazide stimulates renal calcium reabsorption and may cause hypercalcemia. This should be considered when assessing the function of parathyroid glands (see section “Special Precautions”).

Special Instructions

Concomitant use of Ramazid N (12.5/5 mg) with drugs containing aliskiren or with angiotensin II receptor antagonists leading to double blockade of the RAAS is not recommended due to the risk of excessive BP decrease, development of hyperkalemia and worsening of renal function. Simultaneous use of Ramazid N (12.5/5 mg) with drugs containing aliskiren in patients with diabetes and/or renal insufficiency with creatinine clearance <60 ml/min is contraindicated (see section “Contraindications” and “Interaction with other medicinal agents).

Contraindications

• High sensitivity to ramipril or other ACE inhibitors, hydrochlorothiazide, other thiazide diuretics, sulfonamide derivatives or any of the excipients of Ramazide N (12.5/5 mg) (see composition).
• An history of angioedema (hereditary, idiopathic, and related to ACE inhibitor therapy).
• Severe renal failure with creatinine clearance less than 30 mL/min per 1.73 m² body surface area.
• .Hemodialysis or hemofiltration using certain negatively charged membranes such as polyacrylonitrile high-strength membranes (risk of hypersensitivity reactions, including severe anaphylactoid reactions), and low-density lipoprotein apheresis using dextran sulfate (risk of hypersensitivity reactions, including severe anaphylactoid reactions.
• Hemodynamically significant bilateral renal artery stenosis, stenosis of the artery of the sole kidney.
• Clinically significant blood electrolyte imbalances such as hypokalemia, hypomagnesemia or hypercalcaemia (possibility of aggravation when treated with Ramazid N (12.5/5 mg).
• Severe hepatic dysfunction (greater than 9 points on the Child-Pugh scale), hepatic encephalopathy (no clinical experience; it is known that in these conditions minimal electrolyte-water balance disorders may provoke hepatic coma).
• Anuria (due to the presence of hydrochlorothiazide in the drug).
• Pregnancy.
• Breastfeeding period.
• Childhood and adolescence (under 18 years) (insufficient data on efficacy and safety of this drug in children).
• Severe arterial hypotension.
• Simultaneous use with drugs containing aliskiren in patients with diabetes or moderate to severe renal impairment (FFR <60 ml/min/1.73 m²).
• Simultaneous administration with angiotensin II receptor antagonists in patients with diabetic nephropathy.

Caution

• .When Ramazid N (12.5/5 mg) and drugs containing aliskiren or angiotensin II receptor antagonists (dual blockade of the renin-angiotensin-aldosterone system [RAAS] has an increased risk of severe BP reduction, development of hyperkalemia and impaired renal function) are used simultaneously (see
• Conditions accompanied by increased RAAS activity in which ACE inhibitors pose a risk of a sharp decrease in BP with impairment of renal function (see section “Cautionary Note”):
  – severe arterial hypertension, especially malignant arterial hypertension;
  – chronic heart failure, especially severe or for which other medications with hypotensive effect are taken (see section “Special Indications.
  – hemodynamically significant impairment of blood outflow from the left ventricle or blood inflow into the left ventricle (hemodynamically significant stenosis of aortic or mitral valve or hypertrophic obstructive cardiomyopathy [HACCM]);
  – renovascular diseases, including hemodynamically significant unilateral stenosis of the renal artery (careful monitoring of blood creatinine concentration is required, see.
  – previous treatment with diuretics;
  – water-electrolyte balance disorders due to insufficient fluid and/or table salt intake, diarrhea, vomiting, profuse sweating (with inadequate replenishment of fluid and sodium losses).
• In conditions in which excessive BP reduction becomes particularly dangerous (hemodynamically significant stenosis of coronary or cerebral arteries, regular monitoring of the patient’s condition is required, especially at the beginning of treatment with the drug).
• In impaired renal function with a creatinine clearance of 60-30 mL/min per 1.73 m² body surface area due to the risk of hyperkalemia and leukopenia (dosing regimen adjustment required, see “Dosage regimen.
• Following renal transplantation (requires regular monitoring of renal function, especially at baseline, see R & D.
• Hepatic impairment (risk of poor liver function; insufficient clinical experience with this medication, see R & D).
• In case of systemic connective tissue disorders, such as systemic lupus erythematosus or scleroderma (increased risk of immune response, decreased peripheral blood leukocyte count).
• In inhibition of medullary hematopoiesis, concomitant therapy with corticosteroids (glucocorticoids and mineralocorticoids), immunomodulators, cytostatics, antimetabolites, allopurinol, procainamide (increased risk of decreased peripheral blood leukocyte counts, see “Special Precautions.
• Diabetes (risk of hyperkalemia and in case of hypoglycemic drugs (insulin or oral hypoglycemic drugs (sulfonylureas)) – risk of hypoglycemic reactions due to the presence of ramipril in the drug; risk of increased blood glucose concentration due to the presence of hydrochlorothiazide in the drug) (see section “Cautionary Note”, “Side effects”, “Interaction with other medicinal products”).
• In elderly patients (over 65 years) (risk of more pronounced antihypertensive effect, little experience with the drug, more regular monitoring of renal function required).
  

Side effects

Since Ramazid N (12.5/5 mg) is a hypotensive drug, many adverse reactions with its use are secondary to its BP-lowering effect, which may cause reflex activation of the sympathetic nervous system or hyperfusion of various organs. Many other undesirable effects, such as effects on the water-electrolyte balance, some anaphylactoid reactions or mucosal inflammatory reactions, are a consequence of ACE inhibition or other pharmacological effects of ramipril or hydrochlorothiazide.
According to the World Health Organization (WHO), the frequency of adverse reactions is distributed as follows: Very common (>1/10); common (>1/100 to <1/10); infrequent (>1/1000 to <1/100); rare (>1/10 000 to <1/1000); very rare (<1/10 000); frequency unknown (no data available to establish frequency of occurrence).

Cardiac disorders
Infrequent: myocardial ischemia including development of angina pectoris; tachycardia, heart rhythm disorders, palpitations, peripheral edema.
Frequency is unknown: myocardial infarction.

Blood and lymphatic system disorders
Infrequent: decrease of leukocyte number in peripheral blood, decrease of erythrocyte number in peripheral blood, decrease of hemoglobin, hemolytic anemia, decrease of platelet number in peripheral blood.
Frequency is unknown: disorders of medullary hematopoiesis, including agranulocytosis (a sharp decrease or disappearance of granulocytes from peripheral blood), pancytopenia, eosinophilia, hemoconcentration due to reduced fluid content in the body, including in peripheral blood.

Nervous system disorders
Often: headache, dizziness (feeling of “lightness” in the head).
Infrequent: vertigo, paresthesia, tremor, loss of balance, burning sensation of the skin, dysgeusia (taste disorder), agueusia (loss of taste).
Frequency unknown: cerebral ischemia, including ischemic stroke and transient cerebral circulatory disorders; impaired psychomotor reactions, parosmia (olfactory disorders, including subjective sense of smell with its objective absence).

Visual disorders
Infrequent: visual disturbances, including blurred vision, conjunctivitis.
Frequency unknown: xanthopsia, decreased tear fluid production (due to the presence of hydrochlorothiazide in the drug).

Hearing and labyrinth disorders
Infrequent: tinnitus.
Frequency unknown: decreased hearing.

Respiratory system, thoracic and mediastinal organs
Often: unproductive (“dry”) cough, bronchitis.
Infrequent: sinusitis, dyspnea, nasal congestion.
Frequency unknown: bronchospasm, including exacerbation of bronchial asthma symptoms; allergic alveolitis (pneumonitis); noncardiogenic pulmonary edema (due to the presence of hydrochlorothiazide in the drug).

Gastrointestinal tract disorders
Infrequent: inflammatory reactions of mucous membranes of the gastrointestinal tract, digestive disorders, abdominal discomfort, dyspepsia, gastritis, nausea, constipation; gingivitis (due to the presence of hydrochlorothiazide in the drug).
Very rarely: vomiting, aphthous stomatitis, glossitis, diarrhea, epigastric pain, dry oral mucosa.
Frequency unknown: pancreatitis (in exceptional cases when taking ACE inhibitors pancreatitis with fatal outcome is observed); increased activity of “pancreatic” enzymes in blood: angioedema of small intestine; sialoadenitis (due to the presence of hydrochlorothiazide in the drug).

Renal and urinary tract disorders
Infrequent: renal dysfunction, including acute renal failure; increased urine output, increased blood urea concentration, increased blood creatinine concentration (even a slight increase in creatinine concentration with unilateral renal artery stenosis may indicate renal dysfunction).
Frequency unknown: increase of pre-existing proteinuria; interstitial nephritis (due to the presence of hydrochlorothiazide in the drug).
Skin and subcutaneous tissue disorders
Infrequent: angioedema: in exceptional cases, airway obstruction due to angioedema may be fatal; psoriasis-like dermatitis; increased sweating; skin rash, particularly maculopapular skin rash; skin itching; alopecia.
Frequency unknown: toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, pemphigus, worsening of psoriasis, exfoliative dermatitis, photosensitization reaction, onycholysis, pemphigoid or lichenoid exanthema or enanthema, urticaria; systemic lupus erythematosus (due to the presence of hydrochlorothiazide in the drug).
Musculoskeletal and connective tissue disorders
Infrequent: myalgia.
Frequency is unknown: arthralgia, spastic muscle contractions, muscle weakness, muscle rigidity, tetany (due to the presence of hydrochlorothiazide).
Endocrine disorders
Frequency is unknown: syndrome of inadequate secretion of antidiuretic hormone (ADH).
Metabolic and nutrition disorders
Often: decompensation of diabetes mellitus, decreased glucose tolerance, increased concentration of glucose in blood, increased concentration of uric acid in blood, increased gout symptoms, increased concentrations of cholesterol and triglycerides in blood (due to the presence of hydrochlorothiazide in the drug).
Infrequent: anorexia, decreased appetite, decreased potassium content in blood (due to the presence of hydrochlorothiazide in the drug).
Rarely: increase of potassium content in blood (due to the presence of ramipril in the drug).
Frequency is unknown: decreased blood sodium, glucosuria, metabolic alkalosis, hypochloremia, hypomagnesemia, hypercalcemia, dehydration (due to the presence of hydrochlorothiazide).
Vascular disorders
Infrequent: excessive decrease in blood pressure, orthostatic hypotension (impaired orthostatic regulation of vascular tone), fainting state, blood “rushes” to the face.
Frequent unknown: thrombosis with marked fluid loss, vascular stenosis, the occurrence or exacerbation of circulatory disorders against stenotic vascular lesions, Raynaud’s syndrome, vasculitis.
General disorders and disorders at the site of administration
Frequently: increased fatigue, asthenia.
Infrequent: chest pain, increased body temperature.
Immune system disorders
Frequent unknown: anaphylactic or anaphylactoid reactions to ramipril (with ACE inhibition severe anaphylactic or anaphylactoid reactions to insect venom may increase) or anaphylactic reactions to hydrochlorothiazide; increased antinuclear antibody titer.
Liver and biliary tract disorders
Infrequent: cholestatic or cytolytic hepatitis (in exceptional cases with lethal outcome), increased liver enzymes activity and/or increased concentration of conjugated bilirubin in blood; calculous cholecystitis (due to the presence of hydrochlorothiazide in this medicine).
Frequency is unknown: acute hepatic failure, cholestatic jaundice, hepatocellular lesions.
Genital and breast disorders
Infrequent: transient erectile dysfunction.
Frequency unknown: decreased libido, gynecomastia.
Mental disorders
Infrequent: depressed mood, apathy, anxiety, nervousness, sleep disorders (including drowsiness).
Frequency unknown: confusion, anxiety, attention disorders (decreased concentration).

Overdose

Symptoms
In overdose there may be a persistent increase in urine output, excessive peripheral vasodilation (with a marked decrease in BP, development of shock), bradycardia, electrolyte-water balance disorders, renal failure, cardiac rhythm disorders, depression of consciousness, up to coma development; cerebral seizures, paresis and paralytic ileus.

In patients with impaired urine outflow (e.g., prostatic hyperplasia), profuse diuresis may provoke acute urinary retention with bladder overdistension.

Treatment
If possible within the first 30 minutes, gastric lavage should be performed, adsorbents, sodium sulfate should be given. In case of a persistent decrease of blood pressure the administration of alpha1-adrenergic receptor agonists (norepinephrine, dopamine) is indicated in addition to the therapy aimed at replenishment of circulating blood volume and electrolytes. If bradycardia is refractory to drug treatment, a temporary artificial pacemaker may be required. In case of overdose serum concentrations of creatinine and serum electrolyte content should be monitored.

There is no experience regarding the effectiveness of forced diuresis, changes in urine pH, hemofiltration or hemodialysis to accelerate excretion of ramipril and ramiprilat. Hydrochlorothiazide can be excreted by hemodialysis. If hemodialysis or hemofiltration is still intended, the risk of anaphylactoid reactions should be taken into account when using high-flow membranes and do not use them (see section “Contraindications”, “Special notes”, “Interaction with other medicinal products”).

Pregnancy use

Pregnancy

Similarities

Amprilan ND