Enaplus HCT 5/12.5

Rx

Indications

Treatment of mild to moderate hypertension in patients who have been stabilised on the individual components given in the same proportions.

Dosage

The usual dosage range of enalapril is 10 to 40 mg per day administered in a single or two divided doses; hydrochlorothiazide is effective in doses of 12.5 to 50 mg daily.

Dose titration guided by clinical effect

A patient whose blood pressure is not adequately controlled with either enalapril or hydrochlorothiazide monotherapy may be given enalapril maleate and hydrochlorothiazide 5/12.5 mg or enalapril maleate and hydrochlorothiazide 10/25 mg. Further increases of enalapril, hydrochlorothiazide or both depend on clinical response. The hydrochlorothiazide dose should generally not be increased until 2 to 3 weeks have elapsed. In general, patients do not require doses in excess of 20 mg of enalapril or 50 mg of hydrochlorothiazide. The daily dosage should not exceed four tablets of Enaplus HCT 5/12.5 or two tablets of Enaplus HCT 10/25.

Replacement therapy

The combination may be substituted for the titrated components.

Use in renal impairment

The usual regimens of therapy with enalapril maleate and hydrochlorothiazide need not be adjusted as long as the patient’s creatinine clearance is greater than 30 mL/min/1.73 m² (serum creatinine approximately less than or equal to 3 mg/dL or 265 μmol/L). In patients with more severe renal impairment, loop diuretics are preferred to thiazides, so enalapril maleate and hydrochlorothiazide is not recommended.

Usage

Administered orally.

• Hypersensitivity to the active substance(s) or to any of the ingredients.
• Severe renal impairment (creatinine clearance ≤ 30 ml/min).
• Anuria.
• History of angioneurotic oedema associated with previous ACE-inhibitor therapy.
• Hereditary or idiopathic angiooedema.
• Hypersensitivity to sulfonamide-derived drugs.
• Second and third trimesters of pregnancy.
• Severe hepatic impairment.
• Stenosis of the renal arteries.
• The concomitant use of Enaplus HCT 5/12.5 with aliskiren-containing products is contraindicated in patients with diabetes mellitus or renal impairment (GFR < 60 ml/min/1.73 m²).

Very common

• Blurred vision;
• Dizziness;
• Cough;
• Nausea;
• Asthenia.

Common

• Hypokalaemia, increase of cholesterol, increase of triglycerides, hyperuricaemia;
• Headache, depression, syncope, taste alteration;
• Hypotension, orthostatic hypotension, rhythm disturbances, angina pectoris, tachycardia; dyspnoea;
• Diarrhoea, abdominal pain;
• Rash (exanthema) hypersensitivity/angioneurotic oedema (angioneurotic oedema of the face, extremities, lips, tongue, glottis and/or larynx has been reported);
• Muscle cramps;
• Chest pain, fatigue;
• Hyperkalaemia, increases in serum creatinine.

Enalapril maleate – Hydrochlorothiazide

Hypotension and electrolyte fluid imbalance

Regular determination of serum electrolytes should be performed in patient with volume-depleted.

Special attention should be paid to patients with ischemic heart; cerebrovascular disease or severe heart failure.

Renal function impairment

Enaplus HCT 5/12.5 should not be administered to patients with renal insufficiency (creatinine clearance < 80 ml/min. and > 30 ml/min.) until titration of enalapril has shown the need for the dose present in this formulation.

If increase in blood urea and creatinine occurs, therapy with Enaplus HCT 5/12.5 should be discontinued.

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

Dual blockade of RAAS through the combined use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren is not recommended. If dual blockade therapy is considered absolutely necessary, this should only occur under specialist supervision and subject to frequent close monitoring of renal function, electrolytes and blood pressure.

Hyperkalaemia

The combination of enalapril and a low-dose diuretic cannot exclude the possibility of a hyperkalaemia to occur.

Lithium

The combination of lithium with enalapril and diuretic agents is generally not recommended.

Lactose

Enaplus HCT 5/12.5 contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Paediatric population

Safety and efficacy in children has not been established.

Enalapril maleate

Aortic stenosis/Hypertrophic cardiomyopathy

Caution in patients with left ventricular valvular and outflow tract obstruction and avoided in cases of cardiogenic shock and haemodynamically significant obstruction.

Renal function 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.

Renovascular hypertension

In patients with bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney, therapy should be initiated under close medical supervision with low doses, careful titration, and monitoring of renal function.

Haemodialysis patients

The use of enalapril is not indicated in patients requiring dialysis for renal failure.

Kidney transplantation

Treatment with enalapril is not recommended.

Hepatic failure

Patients receiving ACE inhibitors who develop jaundice or marked elevations of hepatic enzymes should discontinue the ACE inhibitor and receive appropriate medical follow-up.

Neutropenia/Agranulocytosis

Extreme caution in patients with collagen vascular disease, immunosuppressant therapy, treatment with allopurinol or procainamide, or a combination of these complicating factors, especially if there is preexisting impaired renal function. Periodic monitoring of white blood cell counts is advised and patients should be instructed to report any sign of infection.

Hyperkalaemia

If concomitant use of enalapril and potassium supplements, potassium-sparing diuretics, or potassium-containing salt substitutes is deemed appropriate, they should be used with caution and with frequent monitoring of serum potassium.

Hypoglycaemia

Closely monitor for hypoglycaemia, especially during the first month of combined use in  diabetic patients treated with oral antidiabetic agents or insulin.

Hypersensitivity/Angioneurotic oedema

Angioneurotic oedema of the face, extremities, lips, tongue, glottis and/or larynx has been reported. In such cases, Enaplus HCT 5/12.5 should be discontinued promptly and appropriate monitoring should be instituted to ensure complete resolution of symptoms prior to dismissing the patient.

Caution in patients with a history of angioedema, patients receiving coadministration of ACE inhibitor and mTOR

Anaphylactoid reactions during hymenoptera desensitisation

These reactions were avoided by temporarily withholding ACE inhibitor therapy prior to each desensitisation.

Anaphylactoid reactions during LDL-apheresis

These reactions were avoided by temporarily withholding ACE inhibitor therapy prior to each apheresis.

Cough

ACE inhibitor-induced cough should be considered as part of the differential diagnosis of cough.

Surgery/Anaesthesia

Enalapril blocks angiotensin II formation and therefore impairs the ability of patients undergoing major surgery or anaesthesia with agents that produce hypotension to compensate via the renin-angiotensin system. Hypotension which occurs due to this mechanism can be corrected by volume expansion.

Hydrochlorothiazide

Renal function impairment

Thiazides may not be appropriate diuretics for use in patients with renal impairment and are ineffective at creatinine clearance values of 30 ml/min or below (i.e., moderate or severe renal insufficiency).

Hepatic disease

Caution in patients with impaired hepatic function or progressive liver disease.

Metabolic and endocrine effects

Thiazide therapy may impair glucose tolerance; decrease serum sodium, magnesium and potassium levels; decrease urinary calcium excretion and cause an intermittent and slight elevation of serum calcium.

Thiazides should be discontinued before testing parathyroid function.

Enalapril may increase urinary uric acid and thus may attenuate the hyperuricaemic effect of hydrochlorothiazide.

Periodic determination of serum electrolytes should be performed at appropriate intervals.

Thiazides can cause fluid or electrolyte imbalance. Caution in patients with cirrhosis of the liver, in patients experiencing brisk diuresis, in patients with inadequate oral intake of electrolytes and in patients receiving concomitant therapy with corticosteroids or ACTH.

Anti-doping test

Hydrochlorothiazide contained in this product can produce a positive analytic result in an anti-doping test.

Hypersensitivity

In patients receiving thiazides, sensitivity reactions may occur with or without a history of allergy and bronchial asthma.

Pregnancy and lactation

Enaplus HCT 5/12.5 is not recommended during the first trimester of pregnancy. Contra-indicated during the second and third trimester of pregnancy.

The use of Enaplus HCT 5/12.5 during breast-feeding is not recommended. If Enaplus HCT 5/12.5 is used during breast-feeding, doses should be kept as low as possible.

Ability to drive and operate machines

When driving vehicles or operating machines it should be taken into account that occasionally dizziness or weariness may occur.