Hypace Tablets 5 mg Tablet.

u2022 HYPACE is indicated in: Hypertension: All grades of essential hypertension and renovascular hypertension.

u2022 Heart failure: HYPACE is indicated for the treatment of symptomatic congestive heart failure, usually in combination with diuretics and digitalis. In these patients HYPACE improves symptoms, increases survival, and decreases the frequency of hospitalization (see Clinical Pharmacology section 5.2, Heart Failure, Mortality trials under section 5 for details).

Asymptomatic left ventricular dysfunction: In clinically stable asymptomatic patients with left ventricular dysfunction (ejection fraction <35%), enalapril decreases the rate of development of overt heart failure and decreases the incidence of hospitalization for heart failure (see Clinical Pharmacology section 5.2, Heart Failure, Mortality trials under Pharmacological Actions section 5 for details).

Since its absorption is not affected by food, HYPACE tablets may be administered before, during or after meals.

Essential hypertension: The initial dose is 10 to 20 mg depending on the degree of hypertension and is given once daily. In mild hypertension the recommended initial dose is 10 mg daily. For other degrees of hypertension, the initial dose is 20 mg daily. The usual maintenance dose is one 20 mg tablet taken once daily. The dosage should be adjusted according to the needs of the patient.

Renovascular hypertension: Since blood pressure and renal function in such patients may be particularly sensitive to ACE-inhibition, therapy should be initiated with a lower starting dose (e.g. 5 mg or less). The dosage should then be adjusted according to the needs of the patient. Most patients may be expected to respond to one 20 mg tablet, taken once daily. For patients with hypertension who have been treated recently with diuretics, caution is recommended (See paragraph above).

Concomitant diuretic therapy in hypertension: Symptomatic hypotension may occur following the initial dose of HYPACE; this is more likely in patients who are being treated currently with diuretics. Caution is recommended, therefore, since these patients may be volume or salt depleted. The diuretic therapy should be discontinued for 2-3 days prior to initiation of therapy with HYPACE. If this is not possible, the initial dose of enalapril should be low (5 mg or less) to determine the initial effect on the blood pressure. Dosage should then be adjusted according to the needs of the patient.

Dosage in Renal Insufficiency: Generally the intervals between the administration of enalapril should be prolonged and/or the dosage reduced.

Renal status
Creatinine Clearance (mL/min)
Initial Dose (mg/day)
Mild impairment
<80
>30
5
Moderate impairment
<30
>10
2,5
Severe impairment
Normally these patients will be on dialysis*
<10
2,5 mg on dialysis days**
* See Special Precautions, Hemodialysis patients.
** Enalaprilat is dialysable. Dosage on non-dialysis days should be adjusted depending on the blood pressure response.

Heart failure/asymptomatic left ventricular dysfunction: The initial dose of HYPACE in patients with symptomatic heart failure or asymptomatic left ventricular dysfunction is 2.5 mg, and it should be administered under close medical supervision to determine the initial effect on the blood pressure. In the absence of, or after effective management of, symptomatic hypotension following initiation of therapy with HYPACE in heart failure, the dose should be increased gradually to the usual maintenance dose of 20 mg daily given as a single dose or two divided doses, as tolerated by the patient. The dose titration may be performed over two to four weeks or more rapidly in the presence of residual signs and symptoms of heart failure. In patients with symptomatic heart failure, this dosage regimen was effective in reducing mortality. Blood pressure and renal function should be monitored closely before and after starting treatment with HYPACE (see SPECIAL PRECAUTIONS section 4.4) because hypotension and consequent renal failure have been reported. In patients treated with diuretics, the dose should be reduced if possible before beginning treatment with HYPACE. The appearance of hypotension after the initial dose of HYPACE does not imply that hypotension will recur during chronic therapy with HYPACE and does not preclude continued use of HYPACE. Serum potassium should also be monitored (see section 4.5).

Hypersensitivity to the product or any of the components and in patients with a history of angioneurotic oedema relating to previous treatment with and angiotensin converting enzyme inhibitor.

Nursing mothers: Enalapril and enalaprilat are secreted in human milk. Caution should be exercised if HYPACE is given to a nursing mother.

Aortic stenosis and hypertrophic cardiomyopathy.

The concomitant use of fluoroquinolones with ACE inhibitors / Angiotensin Receptor Blockers is contraindicated in patients with moderate to severe renal impairment (Creatinine Clearance u2264 30 ml/min) and in elderly patients.

Should a woman become pregnant while receiving an ACE-inhibitor, the treatment must be stopped promptly and switched to a different medicine. Should a woman contemplate pregnancy, the doctor should institute alternative medication. ACE-inhibitors can cause foetal and neonatal morbidity and mortality when administered to pregnant women during the 2nd and 3rd trimesters. ACE-inhibitors pass through the placenta and can be presumed to cause disturbance in foetal blood pressure regulatory mechanisms. Oligohydramnios, which may result in limb contractures, craniofacial deformities and hypoplastic lung development, as well as hypotension, hyperkalemia, oliguria and anuria in newborns have been reported after administration of ACE-inhibitors in the second and third trimester. Cases of defective skull ossification have been observed. Prematurity and low birth mass can occur. Infants whose mothers have taken HYPACE should be closely observed for hypotension, oliguria and hyperkalemia. These adverse effects to the embryo and foetus do not appear to have resulted from intra-uterine ACE-inhibitor exposure limited to the first trimester. Enalapril, which crosses the placenta, has been removed from the neonatal circulation by peritoneal dialysis with some clinical benefit.

Symptomatic hypotension: Symptomatic hypotension was seen in uncomplicated hypertensive patients. In hypertension patients receiving enalapril, hypotension is more likely to occur in if the patient has been volume-depleted e.g. by diuretic therapy, dietary salt restriction, dialysis, diarrhoea or vomiting (see section 4.5 and Side-Effects section 4.8). In patients with heart failure, with or without associated renal insufficiency, symptomatic hypotension has been observed. This is most likely to occur in those with more severe degrees of heart failure, as reflected by the use of high doses of loop diuretics, hyponatraemia or functional renal impairment. In these patients, therapy should be started under medical supervision and the patient should be followed closely whenever the dose of HYPACE and/or diuretic is adjusted. Similar considerations may apply to patients with ischaemic heart or cerebrovascular disease in whom an excessive fall in blood pressure could result in a myocardial infarction or cerebrovascular accident.

If hypotension occurs, the patient should be placed in the supine position and, if necessary, should receive an intravenous infusion of normal saline. A transient hypotensive response is not a contraindication to further doses, which can be given usually without difficulty once the blood pressure has increased after volume expansion. Some patients with congestive heart failure who have normal or low blood pressure, additional lowering of systemic blood pressure may occur with enalapril. This effect is anticipated, and usually is not a reason to discontinue treatment. If hypotension becomes symptomatic, a reduction of dose or discontinuation of HYPACE may be necessary.

Renal Function Impaired: Patients with renal insufficiency may require reduced and/or less frequent doses of HYPACE (see DOSAGE AND DIRECTION FOR USE section 4.2). In some patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney, increases of blood urea and serum creatinine, reversible upon discontinuation of therapy, have been seen. This is especially likely in patients with renal insufficiency. Some patients, with no apparent pre-existing renal disease have developed minor and usually transient increases in blood urea and serum creatinine when enalapril has been given concurrently with a diuretic. Dosage reduction of HYPACE and/or discontinuation of the diuretic may be required.

Hypersensitivity/Angioneurotic oedema: Angioneurotic oedema of the face, extremities, lips, tongue, glottis and/or larynx has been reported in patients treated with angiotensin converting enzymes inhibitors, including enalapril. In such cases, HYPACE should be discontinued promptly and appropriate monitoring should be taken to ensure complete resolution of symptoms prior to dismissing the patient. In those instances where swelling has been confined to the face and lips the condition generally resolved without treatment, although anti-histamines has been useful in relieving symptoms. Angioneurotic oedema associated with laryngeal oedema may be fatal. Where there is involvement of the tongue, glottis or larynx, likely to cause airways obstruction, appropriate therapy such as subcutaneous epinephrine solution 1:1000 (0,3 mL to 0,5 mL) should be administered promptly. Patients with a history of angioedema unrelated to ACE-inhibitor therapy may be at increased risk of angioedema which receiving an ACE-inhibitor. (also see Contra-indications section 4.3)

Anaphylactic reaction during hymenoptera desensitisation: Rarely, patients receiving ACE-inhibitors during desensitisation with hymenoptera venom have experience life threatening anaphylactoid reactions. These reactions were avoided by temporarily withholding ACE-inhibitor therapy prior to each desensitisation.

Haemodialysis patients: Anaphylactoid reactions have been reported in patients dialysed with high-flux membranes (e.g. AN 69u00ae) and treated concomitantly with an ACE-inhibitor. In these patients consideration should be given to using a different type of dialysis membrane or a different class of antihypertensive agent.

Cough: Cough has been reported with the use of ACE-inhibitors. Characteristically, the cough is non-productive, persistent and resolves after discontinuation of therapy. ACE-inhibitor-induced cough should be considered as part of the differential diagnosis of cough.

Surgery/Anaesthesia: In patients undergoing major surgery or during anaesthesia with agents that produce hypotension, enalapril blocks angiotensin-II formation secondary to compensatory renin release. If hypotension occurs and is considered to be due to this mechanism, it can be corrected by volume expansion.

Renal function should be assessed before initiating treatment and monitored during treatment with fluoroquinolones or ACE inhibitors / Angiotensin Receptor Blockers whether used separately and/or concomitantly. Patients currently treated with concomitant use of ACE inhibitors / Angiotensin Receptor Blockers and fluoroquinolones should contact their doctor to re-evaluate their treatment.

Lactose/fructose warning: HYPACE 5 mg contains lactose/fructose which may have an effect on the glycaemic control of patients with diabetes mellitus. HYPACE 5 mg contains lactose/fructose. Patients with the rare hereditary conditions of galactose intolerance e.g. galactosaemia, Lapp lactase deficiency, glucose-galactose malabsorption or fructose intolerance should not take HYPACE 5mg.

Serum potassium: See section 4.1

Paediatric use: Enalapril has not been studied in children.

Antihypertensive Therapy: The combination of HYPACE with other antihypertensive medicines may increase the antihypertensive effect, especially in combination with diuretics. The combination of HYPACE with beta-adrenergic blocking agents and methyldopa or calcium entry blockers potentiates the hypotensive effects of enalapril.

Ganglionic blocking agents or adrenergic blocking agents, combined with HYPACE, should only be administered with careful observation of the patient. Because of lack of experience, concomitant treatment of HYPACE with calcium antagonists is not recommended.

Serum Potassium: Risk factors for the development of hyperkalaemia include renal insufficiency, diabetes mellitus and concomitant use of potassium-sparing diuretics (e.g. spironolactone, triamterene, or amiloride), potassium supplements, or potassium containing salt substitutes. In patients with renal failure the administration of HYPACE may lead to elevation of serum potassium. The use of potassium supplements, potassium sparing diuretics or potassium containing salt substitute particularly in patients with impaired renal function may lead to significant increase in serum potassium. If concomitant use of the above-mentioned agents is deemed appropriate, they should be used with caution and with frequent monitoring of serum potassium.

Serum Lithium: The lithium elimination may be reduced. Therefore, the lithium levels of serum should be carefully compared if lithium salts are to be administered.

Fertility: Should a woman contemplate pregnancy, the doctor should institute alternative medication. (see section 4.4)

Pregnancy: Should a woman become pregnant while receiving an ACE-inhibitor, the treatment must be stopped promptly and switched to a different medicine. ACE-inhibitors can cause foetal and neonatal morbidity and mortality when administered to pregnant women during the 2nd and 3rd trimesters. ACE-inhibitors pass through the placenta and can be presumed to cause disturbance in foetal blood pressure regulatory mechanisms. (see section 4.4)

Breastfeeding: Enalapril and enalaprilat are secreted in human milk. Caution should be exercised if HYPACE is given to a nursing mother. If you are breastfeeding or intend to breastfeed, consult your doctor.

Certain side effects that have been reported with HYPACE may affect some patientsu2019 ability to drive or operate machinery.

Dizziness and headache were the more commonly reported side-effects. Other side-effects occurred and include fatigue, asthenia, hypotension, orthostatic hypotension, syncope, nausea, diarrhoea, muscle cramps, rash, cough, renal dysfunction, renal failure, and oliguria.

Hypersensitivity/angioneurotic oedema: Angioneurotic oedema of the face, which may be fatal, extremities, lips, tongue, glottis and/or larynx have been reported (see Special Precautions).

Cardiovascular: u2022 Myocardial infarction or cerebro-vascular accident, possibly secondary to excessive hypotension in high risk patients (See Special Precautions), chest pain, palpitations, rhythm disturbances, angina pectoris.

Gastrointestinal: u2022 Ileus, pancreatitis, hepatic failure, hepatitis u2013 either hepatocellular or cholestatic jaundice, abdominal pain, vomiting, dyspepsia, constipation, anorexia, stomatitis.

Nervous system/Psychiatric: u2022 Depression, confusion, somnolence, insomnia, nervousness, paraesthesia, vertigo.

Respiratory: u2022 Bronchospasm/asthma, dyspnoea, rhinorrhoea, sore throat and hoarseness pulmonary infiltrates.

Skin: u2022 Diaphoresis, erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, pemphigus, pruritus, urticaria, alopecia, pemphigus.

Others: u2022 Impotence, flushing, taste alteration, tinnitus, glossitis, blurred vision.

A symptom complex has been reported which may include fever, serositis, vasculitis, myalgia/myositis, arthralgia/arthritis, a positive anti-nuclear antibody, elevated erythrocyte sedimentation rate, eosinophilia, and leucocytosis. Rash, photosensitivity or other dermatological manifestations may occur.

Clinical laboratory test findings: Increases in blood urea and serum creatinine, and elevations of liver enzymes and/or serum bilirubin have been seen. These are usually reversible upon discontinuation of enalapril. Hyperkalaemia and hyponatraemia have occurred. Decreases in haemoglobin and haematocrit have been reported.

Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions to SAHPRA via the u201c6.04 Adverse Drug Reactions Reporting Formu201d, found online under SAHPRAu2019s publications. https:///www.sahpra.org.za/publications/index/8

Limited data are available for overdosage in humans. The most prominent feature of overdosage reported to date is marked hypotension, beginning some six hours after ingestion of tablets, concomitant with blockade of the renin-angiotensin system, and stupor. The recommended treatment of overdosage is intravenous infusion of normal saline solution. If ingestion is recent, induce emesis. Enalapril may be removed from the general circulation by haemodialysis.