Enap-H tablets 25 mg + 10 mg 60 pcs. (Hydrochlorothiazide, Enalapril)

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Pharmacological action

Pharmacodynamics

Combined drug whose action is due to the components that make up it has a hypotensive effect.

Enalapril inhibits ACE, which promotes the conversion of angiotensin I to angiotensin II, reduces the concentration of aldosterone in the blood, increases the release of renin by juxtaglomerular cells in the walls of the renal glomerular arterioles, improves the functioning of the kallikrein-kinin system, stimulates the release of prostaglandins and endothelial relaxing factor (NO), inhibits the sympathetic nervous system. Together, these effects eliminate spasm and dilate peripheral arteries, reduce total peripheral vascular resistance, systolic and diastolic blood pressure (BP), post- and preload on the myocardium. Expands arteries to a greater extent than veins, while a reflex increase in heart rate (HR) is not observed.

The antihypertensive effect is more pronounced with a high concentration of renin in blood plasma than with normal or reduced. The decrease in blood pressure in the therapeutic range does not affect cerebral circulation. Improves blood supply to the ischemic myocardium. Enhances renal blood flow, while the glomerular filtration rate does not change. In patients with initially reduced glomerular filtration, its rate usually increases.

The maximum effect of enalapril develops after 6-8 hours and lasts up to 24 hours.

Hydrochlorothiazide is a medium-acting thiazide diuretic. Reduces the reabsorption of sodium ions at the level of the cortical segment of the loop of Henle, without affecting its portion, passing in the brain layer of the kidney. It blocks carbonic anhydrase in the proximal convoluted tubules, enhances the excretion of potassium, bicarbonate and phosphate ions by the kidneys. Virtually no effect on the acid-base state. Increases the excretion of magnesium ions. Delays calcium ions in the body. The diuretic effect develops after 1-2 hours, reaches a maximum after 4 hours, lasts 10-12 hours. The effect decreases with a decrease in glomerular filtration rate and stops when its value is less than 30 ml / min. It reduces blood pressure by reducing the volume of circulating blood (BCC), changes in the reactivity of the vascular wall.

The use of a combination of enalapril and hydrochlorothiazide leads to a more pronounced decrease in blood pressure compared with the monotherapy of each drug separately and allows you to maintain the hypotensive effect of EnapВ® N for at least 24 hours.

Pharmacokinetics of

enalapril. After oral administration, absorption is 60%. Eating does not affect absorption.

Metabolized in the liver to form the active metabolite of enalaprilat, which is a more effective ACE inhibitor than enalapril. Communication with plasma proteins of enalaprilat - 50-60%. The time to reach the maximum concentration (TCmax) of enalapril is 1 hour, enalaprilat is 3-4 hours. Enalaprilat easily passes through the histohematological barriers, excluding the blood-brain barrier, a small amount penetrates the placenta and into breast milk. The renal clearance of enalapril and enalaprilat is 0.005 ml / s (18 l / h) and 0.00225-0.00264 ml / s (8.1-9.5 l / h), respectively. The half-life (T1 / 2) of enalaprilat is 11 hours. It is excreted mainly by the kidneys - 60% (20% - as enalapril and 40% - as enalaprilat), through the intestines - 33% (6% - as enalapril and 27% - in the form of enalaprilat). It is removed during hemodialysis (speed 38-62 ml / min) and peritoneal dialysis, the serum concentration of enalaprilat after 4-hour hemodialysis is reduced by 45-57%.

In patients with impaired renal function, excretion slows down, which requires a dose reduction in accordance with impaired renal function, especially in patients with severe renal failure.

In patients with hepatic insufficiency, the metabolism of enalapril can be slowed down without changing its pharmacodynamic effect.

In patients with chronic heart failure (CHF), the absorption and metabolism of enalaprilat slows down, and the volume of distribution is also reduced.

Hydrochlorothiazide is absorbed mainly in the duodenum and proximal small intestine. Absorption is 70% and increases by 10% when taken with food. The maximum concentration in blood serum is reached after 1.5-5 hours. The volume of distribution is about 3 l / kg. Communication with blood plasma proteins - 40%.

Bioavailability - 70%. In the therapeutic dose range, the average area under the pharmacokinetic curve increases in direct proportion to the dose increase, with the appointment of 1 time per day, cumulation is negligible. Penetrates through the hematoplacental barrier and into breast milk. Accumulates in amniotic fluid. The serum concentration of hydrochlorothiazide in the blood of the umbilical vein is almost the same as in maternal blood. The concentration in the amniotic fluid exceeds that in the blood serum from the umbilical vein (19 times). It is not metabolized in the liver, excreted mainly by the kidneys: 95% unchanged and about 4% in the form of hydrolyzate-2-amino-4-chloro-m-benzenedisulfonamide by glomerular filtration and active tubular secretion in the proximal nephron. The renal clearance of hydrochlorothiazide in healthy volunteers and patients with arterial hypertension is approximately 5.58 ml / s (335 ml / min). Hydrochlorothiazide has a biphasic elimination profile. T1 / 2 in the initial phase is 2 hours, in the final phase (10-12 hours after administration) - about 10 hours.

In elderly patients, hydrochlorothiazide does not adversely affect the pharmacokinetics of enalapril, but the serum concentration of enalaprilat is higher. When prescribing hydrochlorothiazide to patients with heart failure, it was found that its absorption decreases in proportion to the development of heart failure - by 20-70%. T1 / 2 of hydrochlorothiazide increases to 28.9 hours renal clearance is 0.17 - 3.12 ml / s (10-187 ml / min) (average 1.28 ml / s (77 ml / min)).

In patients undergoing intestinal bypass surgery for obesity, absorption of hydrochlorothiazide can be reduced by 30%, and serum concentration by 50%, compared with healthy volunteers.

The simultaneous administration of enalapril and hydrochlorothiazide does not affect the pharmacokinetics of each of them. Buy Enap-H tablets 25 mg + 10 mg 60 pcs. (Hydrochlorothiazide, Enalapril) in newyork free shipping. Fast international shipping USA, AU, EU, UK and others.
Pharmacological action

Pharmacodynamics

Combined drug whose action is due to the components that make up it has a hypotensive effect.

Enalapril inhibits ACE, which promotes the conversion of angiotensin I to angiotensin II, reduces the concentration of aldosterone in the blood, increases the release of renin by juxtaglomerular cells in the walls of the renal glomerular arterioles, improves the functioning of the kallikrein-kinin system, stimulates the release of prostaglandins and endothelial relaxing factor (NO), inhibits the sympathetic nervous system. Together, these effects eliminate spasm and dilate peripheral arteries, reduce total peripheral vascular resistance, systolic and diastolic blood pressure (BP), post- and preload on the myocardium. Expands arteries to a greater extent than veins, while a reflex increase in heart rate (HR) is not observed.

The antihypertensive effect is more pronounced with a high concentration of renin in blood plasma than with normal or reduced. The decrease in blood pressure in the therapeutic range does not affect cerebral circulation. Improves blood supply to the ischemic myocardium. Enhances renal blood flow, while the glomerular filtration rate does not change. In patients with initially reduced glomerular filtration, its rate usually increases.

The maximum effect of enalapril develops after 6-8 hours and lasts up to 24 hours.

Hydrochlorothiazide is a medium-acting thiazide diuretic. Reduces the reabsorption of sodium ions at the level of the cortical segment of the loop of Henle, without affecting its portion, passing in the brain layer of the kidney. It blocks carbonic anhydrase in the proximal convoluted tubules, enhances the excretion of potassium, bicarbonate and phosphate ions by the kidneys. Virtually no effect on the acid-base state. Increases the excretion of magnesium ions. Delays calcium ions in the body. The diuretic effect develops after 1-2 hours, reaches a maximum after 4 hours, lasts 10-12 hours. The effect decreases with a decrease in glomerular filtration rate and stops when its value is less than 30 ml / min. It reduces blood pressure by reducing the volume of circulating blood (BCC), changes in the reactivity of the vascular wall.

The use of a combination of enalapril and hydrochlorothiazide leads to a more pronounced decrease in blood pressure compared with the monotherapy of each drug separately and allows you to maintain the hypotensive effect of EnapВ® N for at least 24 hours.

Pharmacokinetics of

enalapril. After oral administration, absorption is 60%. Eating does not affect absorption.

Metabolized in the liver to form the active metabolite of enalaprilat, which is a more effective ACE inhibitor than enalapril. Communication with plasma proteins of enalaprilat - 50-60%. The time to reach the maximum concentration (TCmax) of enalapril is 1 hour, enalaprilat is 3-4 hours. Enalaprilat easily passes through the histohematological barriers, excluding the blood-brain barrier, a small amount penetrates the placenta and into breast milk. The renal clearance of enalapril and enalaprilat is 0.005 ml / s (18 l / h) and 0.00225-0.00264 ml / s (8.1-9.5 l / h), respectively. The half-life (T1 / 2) of enalaprilat is 11 hours. It is excreted mainly by the kidneys - 60% (20% - as enalapril and 40% - as enalaprilat), through the intestines - 33% (6% - as enalapril and 27% - in the form of enalaprilat). It is removed during hemodialysis (speed 38-62 ml / min) and peritoneal dialysis, the serum concentration of enalaprilat after 4-hour hemodialysis is reduced by 45-57%.

In patients with impaired renal function, excretion slows down, which requires a dose reduction in accordance with impaired renal function, especially in patients with severe renal failure.

In patients with hepatic insufficiency, the metabolism of enalapril can be slowed down without changing its pharmacodynamic effect.

In patients with chronic heart failure (CHF), the absorption and metabolism of enalaprilat slows down, and the volume of distribution is also reduced.

Hydrochlorothiazide is absorbed mainly in the duodenum and proximal small intestine. Absorption is 70% and increases by 10% when taken with food. The maximum concentration in blood serum is reached after 1.5-5 hours. The volume of distribution is about 3 l / kg. Communication with blood plasma proteins - 40%.

Bioavailability - 70%. In the therapeutic dose range, the average area under the pharmacokinetic curve increases in direct proportion to the dose increase, with the appointment of 1 time per day, cumulation is negligible. Penetrates through the hematoplacental barrier and into breast milk. Accumulates in amniotic fluid. The serum concentration of hydrochlorothiazide in the blood of the umbilical vein is almost the same as in maternal blood. The concentration in the amniotic fluid exceeds that in the blood serum from the umbilical vein (19 times). It is not metabolized in the liver, excreted mainly by the kidneys: 95% unchanged and about 4% in the form of hydrolyzate-2-amino-4-chloro-m-benzenedisulfonamide by glomerular filtration and active tubular secretion in the proximal nephron. The renal clearance of hydrochlorothiazide in healthy volunteers and patients with arterial hypertension is approximately 5.58 ml / s (335 ml / min). Hydrochlorothiazide has a biphasic elimination profile. T1 / 2 in the initial phase is 2 hours, in the final phase (10-12 hours after administration) - about 10 hours.

In elderly patients, hydrochlorothiazide does not adversely affect the pharmacokinetics of enalapril, but the serum concentration of enalaprilat is higher. When prescribing hydrochlorothiazide to patients with heart failure, it was found that its absorption decreases in proportion to the development of heart failure - by 20-70%. T1 / 2 of hydrochlorothiazide increases to 28.9 hours renal clearance is 0.17 - 3.12 ml / s (10-187 ml / min) (average 1.28 ml / s (77 ml / min)).

In patients undergoing intestinal bypass surgery for obesity, absorption of hydrochlorothiazide can be reduced by 30%, and serum concentration by 50%, compared with healthy volunteers.

The simultaneous administration of enalapril and hydrochlorothiazide does not affect the pharmacokinetics of each of them.

Indications

Arterial hypertension (for patients who are shown combination therapy).

Contraindications

- hypersensitivity (including to individual components of the drug or sulfonamide derivatives)

- anuria, severe renal dysfunction (creatinine clearance (CC) less than 30 ml / min)

- a history of angioedema associated with the use of previously ACE inhibitors, as well as hereditary or idiopathic angioedema

- bilateral renal artery stenosis, s stenosis of a single kidney pregnancy and lactation

- under 18 years of age (efficacy and safety not established)

- lactose intolerance, lactase deficiency or glucose-galactose malabsorption.

Use during pregnancy and lactation

Enap® N is contraindicated in pregnancy.

The effects of ACE inhibitors on the fetus in the first trimester of pregnancy have not been established. The use of ACE inhibitors in the second and third trimesters of pregnancy was accompanied by a negative effect on the fetus and newborn.

Newborns developed arterial hypotension, renal failure, hyperkalemia, and / or hypoplasia of the skull bones. Perhaps the development of oligohydramnios, apparently due to impaired renal function of the fetus. This can lead to contracture of the extremities, deformation of the bones of the skull, including its facial part, and hypoplasia of the lungs.

The use of diuretics during pregnancy is not recommended, as it can cause fetal and newborn jaundice, thrombocytopenia, and possibly other, adverse reactions observed in adults.

Enalapril and hydrochlorothiazide pass into breast milk. Therefore, when prescribing the drug Enap® N during lactation, it is necessary to abandon breastfeeding.

Special instructions

Arterial hypotension

Arterial hypotension with all the clinical consequences can occur after the first use of EnapВ® H tablets in patients with severe heart failure and hyponatremia, severe renal failure or left ventricular dysfunction, and especially in patients with hype as a result of diuretic therapy, a salt-free diet, diarrhea, vomiting, or hemodialysis.

In case of arterial hypotension, it is necessary to lay the patient on his back with a low headboard and, if necessary, adjust the volume of the bcc by infusion of a solution of 0.9% sodium chloride. Arterial hypotension that occurs after taking the first dose is not a contraindication for further treatment.

Caution is required in patients with coronary heart disease, severe cerebrovascular disease, aortic stenosis or idiopathic hypertrophic obstructive subaortic stenosis, which prevents outflow of blood from the left ventricle, severe atherosclerosis, in elderly patients as a result of the risk of arterial hypotension and poor blood supply and kidneys.

Water-electrolyte imbalance

Regular monitoring of serum electrolyte concentrations during treatment is necessary to identify possible imbalances and timely measures are taken. Determination of serum concentration of electrolytes is mandatory for patients with prolonged diarrhea, vomiting.

In patients taking EnapВ® N, it is necessary to detect signs of impaired water-electrolyte balance, such as dry mouth, thirst, weakness, drowsiness, increased irritability, myalgia and cramps (mainly calf muscles), decreased blood pressure, tachycardia, oliguria and gastrointestinal disturbances (nausea, vomiting).

Impaired renal function

EnapВ® N in patients with renal failure (CC 30-75 ml / min) should be used only after preliminary titration of enalapril and hydrochlorothiazide separately, respectively, in doses of the combined preparation EnapВ® N.

Impaired liver function

Enap® N should be used with caution in patients with hepatic insufficiency or progressive liver disease, since hydrochlorothiazide can cause hepatic coma even with minimal disturbances in water-el ktrolitnyh balance. Several cases of the development of acute liver failure with cholestatic jaundice, fulminant necrosis of the liver and death (rarely) during treatment with ACE inhibitors have been reported. In case of jaundice and increased activity of “liver” transaminases, treatment with Enap® N should be stopped immediately, patients should be monitored.

Metabolic and endocrine effects

Caution is necessary in all patients receiving treatment with hypoglycemic agents for oral administration or insulin, since hydrochlorothiazide can weaken, and enalapril enhance their effect.

Thiazide diuretics can reduce kidney excretion of calcium and cause a slight and transient increase in serum calcium.

Severe hyperkalemia may be a sign of latent hyperparathyroidism. Before conducting a study of the function of the parathyroid glands, thiazide diuretics must be canceled.

During treatment with thiazide diuretics, serum cholesterol and triglyceride concentrations may increase.

Thiazide diuretic therapy in some patients may exacerbate hyperuricemia and / or exacerbate the course of gout. However, enalapril enhances the excretion of uric acid by the kidneys, thereby counteracting the hyperuricemic effect of hydrochlorothiazide.

Allergic reactions / Angioneurotic edema

If angioedema of the face occurs, it is usually enough to cancel therapy and prescribe antihistamines to the patient.

Angioedema of the tongue, pharynx or larynx may be fatal. With angioedema of the tongue, pharynx or larynx, which can lead to airway obstruction, epinephrine (0.3-0, 5 ml of a solution of epinephrine (adrenaline) subcutaneously in a ratio of 1: 1000) and maintain airway patency (intubation or tracheostomy).

Among patients of the Negroid race receiving therapy with an ACE inhibitor, the incidence of angioedema is higher than among patients of a different race.

Patients with a history of angioedema not associated with ACE inhibitors have an increased risk of developing angioedema with any ACE inhibitor.

In patients taking thiazide diuretics, hypersensitivity reactions can develop both in the presence and in the absence of a history of allergic reactions. A deterioration in the course of systemic lupus erythematosus has been reported.

Due to the increased risk of anaphylactic reactions, the drug EnapВ® N should not be prescribed to patients hemodialysis using high-flow polyacrylonitrile membranes (AN69В®) undergoing apheresis of low-density lipoproteins with dextransulfate and immediately before the desensitization procedure for aspen or bee venom.

Surgery / General Anesthesia

Prior to surgery (including dentistry), the anesthetist should be advised of the use of ACE inhibitors.

During surgery or during general anesthesia using hypotensive medications, ACE inhibitors can block the formation of angiotensin II in response to compensatory release of renin. If at the same time a marked decrease in blood pressure develops, due to a similar mechanism, it can be corrected by an increase in the volume of circulating blood.

Cough

Cough was observed with ACE inhibitors. The cough is dry, long, which disappears after stopping the use of ACE inhibitors. With a differential diagnosis of cough, cough caused by the use of ACE inhibitors should be considered.

Effect on the ability to drive a vehicle and other mechanical means: At the beginning of treatment with EnapВ® N, a marked decrease in blood pressure, dizziness and drowsiness may occur, which may reduce the ability to drive vehicles, engage in other potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions. Therefore, at the beginning of treatment, it is not recommended to drive vehicles and engage in other potentially dangerous activities, requiring increased concentration of attention and speed of psychomotor reactions.

Composition

For 1 tablet:

Active ingredients:

Hydrochlorothiazide 25, 00 mg

Enalapril maleate 10.00 mg

Excipients: sodium bicarbonate 5.10 mg, lactose monohydrate 120.02 mg, corn starch 29.60 mg, pregelatinized starch 6.00 mg, talc 6.00 mg, magnesium stearate 2 , 00 mg, quinoline yellow dye, Е104 0.06 mg

Dosage and administration

EnapВ® N should be taken regularly at the same time, preferably in the morning, during or after a meal, without chewing, with a small amount of liquid. The recommended dose is 1 tablet per day.

In patients undergoing diuretic therapy, it is recommended to cancel treatment or reduce the dose of diuretics at least 3 days before the start of treatment with EnapВ® N to prevent the development of symptomatic arterial hypotension.

Renal function should be investigated before treatment begins.

Duration of treatment is determined by the physician.

Dose for impaired renal function

In patients with renal insufficiency with a CC of 30-75 ml / min, EnapВ® N should be used only after preliminary titration of doses of enalapril and hydrochlorothiazide separately, respectively, in doses combined with EnapВ® N.

Side effects of

Classification of the incidence of side effects of the World Health Organization (WHO):

- very often (> 1/10)

- often (> 1/100 and - infrequently (> 1/1000 and - rarely (> 1 / 10000 and - very rarely (From the hematopoietic system and lymphatic system:

- rarely: neutropenia, decreased hemoglobin and hematocrit, thrombocytopenia, leukopenia, inhibition of bone marrow function

Metabolic and nutritional disorders

- infrequently: gout

From the central nervous system:

- very common: dizziness, srd weakness lkp - often: headache, asthenia

- infrequently: insomnia, drowsiness, paresthesia, irritability

From the sensory organs:

- infrequently: tinnitus

From the cardiovascular system

- often: orthostatic hypotension

- infrequently: fainting, marked decrease in blood pressure, sensation of palpitations, tachycardia, chest pain

system:

- often: cough

- rarely: shortness of breath

Digestive system:

- often: nausea

- rarely: diarrhea, vomiting, dyspepsia, abdominal pain, flatulence, constipation, dry mouth

- rarely: , fulminant necrosis

alle nological reaction:

- rare: Stevens-Johnson syndrome

- rare: angioneurotic edema

- very rare: intestinal angioedema

swelling of part of the skin:

- Uncommon: skin rash, itching, increased sweating, skin necrosis, alopecia

From the genitourinary system:

- infrequently: impaired renal function, acute renal failure, impotence, decreased libido

From the musculoskeletal system:

- often: muscle spasms

indicators:

- rarely: hyperglycemia, hyperuricemia, hypokalemia, hyperkalemia, hyponatremia, increased serum urea and creatinine, increased activity of hepatic transaminases and

bilirubin Other:

- opi the dignity is a symptom complex, which may include fever, myalgia and arthralgia, serositis, vasculitis, an increase in the erythrocyte sedimentation rate, leukocytosis and eosinophilia, a skin rash, a positive test for antinuclear antibodies.

Drug Interactions

Serum Potassium

Use of potassium supplements, potassium-sparing agents, or potassium-containing salt substitutes, especially in patients with renal failure, can lead to a significant increase in serum potassium. Potassium loss with thiazide diuretics is usually reduced by enalapril. Serum potassium usually remains within the normal range.

Lithium

When used simultaneously with lithium preparations, slowing down lithium excretion (enhancing the cardiotoxic and neurotoxic effects of lithium).

Non-depolarizing muscle relaxants

Thiazide diuretics can enhance the effect of tubocurarine chloride.

Narcotic analgesics / antipsychotics

The simultaneous use of thiazide diuretics, narcotic analgesics or phenothiazine derivatives can lead to orthostatic hypotension.

Other antihypertensive agents

The use of beta-blockers, alpha-blockers, ganglioblockers, methyldopa or “slow” calcium channel blockers together with enalapril can further reduce blood pressure.

Allopurinol, cytostatics, and immunosuppressants

Concomitant use with ACE inhibitors may increase the risk of leukopenia.

Glucocorticosteroids, calcitonin

Concomitant use of thiazide diuretics can lead to the development of hypokalemia.

Cyclosporine

Concomitant use with ACE inhibitors may increase the risk of hyperkalemia.

Nonsteroidal anti-inflammatory drugs

The simultaneous use of non-steroidal anti-inflammatory drugs (NSAIDs) (including selective cyclooxygenase-2 inhibitors) can weaken the antihypertensive effect of ACE inhibitors.

NSAIDs and ACE inhibitors have an additive effect on increasing serum potassium, which can lead to impaired renal function, especially in patients with impaired renal function. This effect is reversible.

NSAIDs may decrease the diuretic and antihypertensive effects of diuretics.

Antacids

Antacids may decrease the bioavailability of ACE inhibitors.

Sympathomimetics may reduce the antihypertensive effect of ACE inhibitors.

Thiazide diuretics may reduce the effects of adrenergic agonists (epinephrine).

Ethanol enhances the hypotensive effect of ACE inhibitors and thiazide diuretics, which can cause orthostatic hypotension.

Hypoglycemic agents for oral administration and insulin

Epidemiological studies suggest that the simultaneous use of ACE inhibitors and hypoglycemic agents can lead to hypoglycemia. More often hypoglycemia develops in the first weeks of therapy in patients with impaired renal function. Long-term and controlled clinical studies of enalapril do not confirm these data and do not limit the use of enalapril in patients with diabetes mellitus. However, such patients should be under regular medical supervision.

The use of hypoglycemic agents for oral administration and insulin with thiazide diuretics may require dose adjustment.

Colestyramine and colestipol

A single dose of colestyramine or colestipol reduces the absorption of hydrochlorothiazide in the gastrointestinal tract by 85% and 43%, respectively.

Gold preparations

With the simultaneous use of ACE inhibitors and gold preparations (sodium aurothiomalate) intravenously, a symptom complex has been described, including facial flushing, nausea, vomiting and hypotension.

Overdose

Symptoms: increased diuresis, marked decrease in blood pressure with bradycardia or other heart rhythm disturbances, seizures, impaired consciousness (including coma), acute renal acid and renal failure, acute renal acid and renal failure, blood balance.

Treatment: the patient is transferred to a horizontal position with raised legs. In mild cases, gastric lavage and ingestion of activated charcoal are indicated, in more serious cases, measures aimed at stabilizing blood pressure - intravenous administration of plasma substitutes, infusion of 0.9% sodium chloride solution. The patient needs to control the level of blood pressure, heart rate, respiratory rate, serum concentration of urea, creatinine, electrolytes and diuresis, if necessary, intravenous administration of angiotensin II, hemodialysis (enalaprilate excretion rate - 62 ml / min).

Storage conditions

In a dry place, at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Term hodnosty

5 years

Deystvuyuschee substances

Hydrohlorotyazyd, enalapril

Dosage form

tablet

KRKA d.d. Novo mesto AO, Slovenia



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