Enaboston 20 Plus

DOSAGE AND ADMINISTRATION

Administration: 

Tablets are engraved with a scoreline to divide into 2 equal doses.

Oral use. Take 1 tablet once daily in the morning. If blood pressure response is inadequate at the end of the dosing interval, the dosage could be considered dividing into twice daily. Do not take the medicine after 6pm.

Dosage:

To minimize adverse effects caused by both medicines, combination therapy should be instituted initially after failure to control blood pressure with monotherapy. Usual therapeutic dose of enalapril is 5 – 40 mg, of hydrochlorothiazide is 12,5 – 50 mg. Increasing the dose should be based on the patient's response and tolerability, and the response should be monitored for 2 to 3 weeks before increasing the dose.

Symptomatic hypotension may occur following the initial dose of Enaboston plus; this is more likely in patients who are volume-depleted as a result of prior diuretic therapy. Therefore, the diuretic therapy should be discontinued for 2-3 days prior to initiation of therapy with Enaboston plus.

In addition, Enaboston plus can be used as a substitute for two separate preparations of enalapril and hydrochlorothiazide at equivalent doses.

Treatment for special patients

Renal impairment: No dose adjustment is necessary for patients with renal impairment whose creatinine clearance is more than 30 ml/min. In patients with severe renal insufficiency, loop diuretics (as furosemide) are more suitable than thiazide diuretics. Therefore, the combination of enalapril maleate and hydrochlorothiazide should not be recommended.

CONTRAINDICATIONS

Hypersensitivity to any of the excipients and other sulfonamide derivatives.

Patients with History of angioneurotic oedema associated with previous ACE-inhibitor therapy, hereditary or idiopathic angioedema.

Patients with anuria, bilateral renal artery stenosis or renal artery stenosis in person with a solitary kidney (one kidney).

Second and third trimesters of pregnancy.

Severe hepatic impairment or severe renal impairment (creatinine clearance ≤30 ml/min).

The concomitant use with aliskiren-containing products is contraindicated in patients with diabetes mellitus or renal impairment (ClCr <60 ml/min)

WARNINGS AND PRECAUTIONS

Precations in use

Hypotension

Symptomatic hypotension is rarely seen in uncomplicated hypertensive patients, but more likely to occur if the patient has been volume–depleted caused by diuretic therapy or hemodialysis. In hypertensive patients with severe congestive heart failure, with or without associated renal insufficiency, symptomatic hypotension has been observed and may be accompanied by oliguria or azotemia, potentially leading to acute renal failure and/or death.

These patients should be closely monitored during the first 2 weeks of treatment and when the dose is increased. It also should be careful when administering the drug to patients with ischemic heart disease or with cerebrovascular disease, because excessive hypotension may precipitate myocardial infarction or cerebrovascular accident.

Hypersensitivity and anaphylactoid reactions

Angioedema

Angioneurotic oedema of the face, extremities, lips, tongue, glottis and/or larynx has been reported in patients treated with angiotensin-converting enzyme inhibitors, including enalapril maleate. This may occur at any time during treatment. 

In such cases, it should be discontinued promptly and appropriate monitoring should be instituted to ensure complete resolution of symptoms.

Coadministration with mTOR inhibitor (e.g., temsirolimus, sirolimus, everolimus) or neprilysin inhibitor may increase the risk for angioedema caused by enalapril.

Intestinal angioedema

Intestinal angioedema has also been reported in patients receiving ACE inhibitors. Patients often have abdominal pain (with or without vomiting) that resolve spontaneously upon discontinuation of the drug. Attention should be paid to the differential diagnosis of drug-induced intestinal edema from common abdominal pain. Diagnostic measures can be applied such as sonography or CT scan of the abdomen.

Patients with a history of angioedema unrelated to an ACE inhibitor remain at high risk for angioedema when using an ACE inhibitor.

Anaphylactoid reactions

Some patients have experienced life-threatening anaphylactic reactions because of receiving ACE inhibitors during desensitization to insect venom, hemodialysis with polyacrylonitrile or low-density lipoprotein (LDL) apheresis with dextran sulfate. These reactions were avoided by temporarily withholding ACE inhibitor therapy prior to each desensitization or LDL apheresis. For patients on hemodialysis, a different type of membrane filter or a different antihypertensive medicine should be considered.

Renal impairment

Renal failure has been reported in association with enalapril and has been mainly in patients with severe heart failure or underlying renal disease, including renal artery stenosis. If recognized promptly and treated appropriately, renal failure

when associated with therapy with enalapril is usually reversible.

Some hypertensive patients with no apparent pre-existing renal disease have developed increases in blood urea (BUN) and creatinine when enalapril has been given concurrently with hydrochlorothiazide. If this occurs, the dose reduction of enalapril and/or the discontinuation of hydrochlorothiazide should be considered.

Hepatic impairment

ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice or hepatitis and progresses to fulminant hepatic necrosis and death. The mechanism of this syndrome is not understood. Patients receiving ACE inhibitors who develop jaundice or marked elevations of hepatic enzymes should discontinue the ACE inhibitor and receive appropriate medical follow-up. In addition, Enaboston plus should be used with caution in patients with impaired hepatic function or progressive liver disease, since minor alterations of fluid and electrolyte balance may precipitate hepatic coma.

Neutropenia/Agranulocytosis

Neutropenia/agranulocytosis, thrombocytopenia and anemia have been reported in patients receiving ACE inhibitors but occur rarely in patients with normal renal function and no other complicating factors. Enalapril should be used with extreme caution in patients with collagen vascular disease, immunosuppressant therapy, treatment with allopurinol or procainamide, especially if there is pre-existing impaired renal function. Periodic monitoring of white blood cell counts is advised and patients should be instructed to report any sign of infection.

Dual blockade of the renin-angiotensin-aldosterone system (RAAS)

Clinical trial data have shown that dual blockade of the renin-angiotensin-aldosterone-system (RAAS) through the combined use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren is associated with a higher frequency of adverse events such as hypotension, hyperkalemia and acute renal failure but do not increase efficacy when compared to monotherapy.

Therefore, the combination of the above drugs is not recommended, especially in patients with diabetic nephropathy.

Cough

Cough has been reported with the use of ACE inhibitors. Characteristically, the cough is non-productive, persistent and resolves after discontinuation of therapy. The differential diagnosis between cough caused by ACE inhibitor use and common cough should be noted.

Surgery/Anaesthesia

In patients undergoing major surgery or anesthesia with agents that produce hypotension, enalapril blocks angiotensin II formation, making patients experience hypotension. Hypotension that occurs due to this mechanism can be corrected by fluid compensation, volume expansion.

Ethnic Differences

Black patients receiving ACE inhibitors have been reported to have a higher incidence of angioedema compared to other ethnicities. Moreover, enalapril is apparently less effective in lowering blood pressure in black people than in non-blacks, possibly because of a higher prevalence of low-renin states in the black hypertensive population.

Electrolyte Fluid Imbalance

Hyperkalemia may occur with ACE inhibitors alone but is less common when used in combination with hydrochlorothiazide. Risk factors for the development of hyperkalemia include those with renal insufficiency, diabetes mellitus, and concomitant use of potassium-sparing diuretics, food or medicine containing potassium.

The drug contains a thiazide diuretic, so it can also cause hypokalemia, especially when patients have severe cirrhosis or after prolonged use. Due to opposing pharmacological properties, the combination of enalapril with hydrochlorothiazide reduces the risk of hypokalemia as a side effect of each drug.

In addition, hydrochlorothiazide causes hyponatremia and hypochloremia, often accompanied by metabolic alkalosis. Patients should be periodically monitored for electrolytes in serum and urine, especially patients taking corticosteroids, ACTH or digitalis, quinidine (risk of torsades de pointes causing ventricular fibrillation); the patient is vomiting or receiving intravenous therapy.

Metabolic disorder

Thiazide therapy may impair glucose tolerance. Dosage adjustment of antidiabetic agents, including insulin, may be required.

Increases in cholesterol and triglyceride levels have been reported with patients using thiazide diuretic therapy. Therefore, it should be used with caution in people with moderate or high blood cholesterol, and high blood triglycerides.

This medicine can also precipitate hyperuricemia and worsen gout.

Acute myopia and secondary angle-closure glaucoma

Hydrochlorothiazide, a sulfonamide, may induce an anomalous reaction, resulting in patients developing transient myopia and acute secondary angle-closure glaucoma. Symptoms include blurred vision or eye pain, which usually appear within hours to weeks of starting the medication. If not treated in time, the patient can lose their vision permanently.

Systemic lupus erythematosus

Hydrochlorothiazide promotes or worsens systemic lupus erythematosus.

Precautions with excipients

This product contains lactose, therefore, do not use for patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency of glucose-galactose malabsorption.

Sodium

This product contains less than 1 mmol sodium (23 mg, in a tablet), that is to say essentially ‘sodium-free’

SHELF-LIFE 

36 months from the manufacturing date.

Box of 02 blisters x 10 tablets