Consumer medicine information

APO-Enalapril

Enalapril maleate

BRAND INFORMATION

Brand name

APO-Enalapril

Active ingredient

Enalapril maleate

Schedule

What is in this leaflet

This leaflet answers some common questions about this medicine. It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking this medicine against the benefits they expect it will have for you.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine. You may need to read it again.

What this medicine is used for

Enalapril is used to treat:

heart failure
high blood pressure (also known as hypertension)

Enalapril belongs to a group of medicines called Angiotensin Converting Enzyme (ACE) inhibitors.

One of the ways enalapril helps lower blood pressure and treat heart failure is that it widens blood vessels.

This means that blood is able to pass through them more easily and the heart doesn't have to pump as hard to move blood around the body. This also means that when you place extra demands on your heart, such as during exercise, the heart may cope better so you may not get short of breath as easily.

Hypertension
Everyone has blood pressure. This pressure helps get your blood all around your body. Your blood pressure may be different at different times of the day, depending on how busy or worried you are. You have hypertension (high blood pressure) when your blood pressure stays higher than is needed, even when you are calm and relaxed.

There are usually no symptoms of hypertension. The only way of knowing that you have hypertension is to have your blood pressure checked on a regular basis. If high blood pressure is not treated it can lead to serious health problems. You may feel fine and have no symptoms, but eventually hypertension can cause stroke, heart disease and kidney failure.

Heart Failure
Heart failure means that the heart muscle cannot pump blood strongly enough to supply all the blood needed throughout the body. Heart failure is not the same as heart attack and does not mean that the heart stops working. Heart failure may start off with no symptoms, but as the condition progresses, patients may feel short of breath or may get tired easily after light physical activities, such as walking.

Fluid may also collect in different parts of the body, often first noticed as swollen ankles and feet.

Enalapril helps to treat heart failure, whether you have symptoms or not. It does this by helping to stop the heart muscle from getting weaker. It may also slow down the development of symptoms, such as shortness of breath, tiredness after light physical activity, or swelling of the ankles and feet. By slowing down the progression of heart failure, enalapril reduces the chance of having a heart attack, or needing to go to hospital as a result of heart failure.

Ask your doctor if you have any questions about why this medicine has been prescribed for you. Your doctor may have prescribed this medicine for another reason.

This medicine is available only with a doctor's prescription.

There is no evidence that this medicine is addictive.

This medicine should not be used in children.

Before you take this medicine

When you must not take it

Do not take this medicine if you have an allergy to:

any medicine containing enalapril or any other ACE inhibitor
any of the ingredients listed at the end of this leaflet

Some of the symptoms of an allergic reaction may include:

shortness of breath
wheezing or difficulty breathing
swelling of the face, lips, tongue or other parts of the body
rash, itching or hives on the skin

Do not take this medicine if you have a history of swelling of the face, lips, tongue, throat, hands or feet, for no apparent reason.

Do not take this medicine if you have diabetes while also taking aliskiren for blood pressure control.

Do not take this medicine if you are taking a medicine containing a neprilysin inhibitor (e.g. sacubitril). Do not take enalapril for at least 36 hours before or after you take any medicine containing a neprilysin inhibitor (e.g. sacubitril) or combinations including these medicines (e.g. sacubitril/valsartan).

Do not take this medicine if you are pregnant. Enalapril may affect your developing baby if you take it during pregnancy.

Do not breastfeed if you are taking this medicine. Enalapril may pass into breast milk and there is a possibility that your baby may be affected.

If you are not sure whether you should start taking this medicine, talk to your doctor.

Before you start to take it

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you have or have had any of the following medical conditions:

kidney disease, or are undergoing dialysis
diabetes
heart problems

Tell your doctor if you are pregnant or plan to become pregnant or are breastfeeding. This medicine should not be used during pregnancy or while breastfeeding.

Tell your doctor if you have recently suffered from excessive vomiting or diarrhoea.

Tell your doctor if you are following a very low salt diet.

Tell your doctor if you are taking potassium supplements, potassium-sparing agents, potassium-containing salt substitutes or other drugs that may increase serum potassium (e.g. trimethoprim-containing products).

Tell your doctor if you suffer from low blood pressure. You may notice this as faintness or dizziness, especially when standing.

Tell your doctor if you are planning to have surgery and anaesthesia (even at the dentist's office). You may experience a sudden fall in blood pressure associated with anaesthesia.

If you have not told your doctor about any of the above, tell them before you start taking this medicine.

Taking other medicines

Tell your doctor or pharmacist if you are taking any other medicines, including any that you get without a prescription from your pharmacy, supermarket or health food shop.

Some medicines may interact with enalapril. These include:

other blood pressure medicines (some medications are not recommended while taking enalapril – speak to your doctor to confirm)
diuretic tablets – also called fluid or water tablets
lithium, used to treat mood swings and some types of depression
potassium tablets
potassium-containing salt substitutes
potassium-sparing agents (e.g. spironolactone, eplerenone, triamterene or amiloride)
other drugs that may increase serum potassium levels (e.g. trimethoprim-containing products)
non-steroidal anti-inflammatory medicines (NSAIDs or COX-2 inhibitors), used to relieve pain, swelling and other symptoms of inflammation
arthritis medicines, including gold therapy
insulin or oral anti-diabetic medicines – you should be closely monitored for low blood glucose levels, especially during the first month of treatment with enalapril
mTOR inhibitors (e.g. temsirolimus, sirolimus or everolimus)
a medicine containing a neprilysin inhibitor (e.g. sacubitril)

These medicines may be affected by enalapril or may affect how well it works. You may need different amounts of your medicines, or you may need to take different medicines.

Other medicines not listed above may also interact with enalapril.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking this medicine.

How to take this medicine

Follow carefully all directions given to you by your doctor. They may differ from the information contained in this leaflet.

If you do not understand the directions, ask your doctor or pharmacist for help.

How much to take

Your doctor will tell you how much of this medicine you should take. This will depend on your condition and whether you are taking any other medicines.

If you are over the age of 65 years, your doctor may start you on a lower dosage.

For high blood pressure:
For most patients, the usual starting dose is 5 mg taken once a day. Some patients may need a lower starting dose. The dose may need to be increased depending on your blood pressure. Most patients take between 10 to 40 mg each day.

For heart failure:
The usual starting dose is 2.5 mg taken once a day. Depending on your response, this dose may need to be increased up to 20 mg each day. This dose may be taken once a day or divided into two doses per day.

How to take it

Swallow the tablets with a glass of water.

When to take it

Take your medicine at about the same time each day. Taking it at the same time each day will have the best effect. It will also help you remember when to take it.

It does not matter if you take this medicine before or after food.

How long to take it for

Continue taking your medicine for as long as your doctor tells you.

This medicine helps to control your condition but does not cure it. It is important to keep taking your medicine every day, even if you feel well.

Make sure you have enough to last over weekends and holidays.

If you forget to take it

If it is almost time to take your next dose, skip the dose you missed and take your next dose when you are meant to.

Otherwise, take it as soon as you remember, and then go back to taking your medicine as you would normally.

Do not take a double dose to make up for the dose that you missed. This may increase the chance of you getting an unwanted side effect.

If you are not sure what to do, ask your doctor or pharmacist.

If you have trouble remembering to take your medicine, ask your pharmacist for some hints.

If you take too much (overdose)

Immediately telephone your doctor or the Poisons Information Centre (telephone 13 11 26) for advice or go to Accident and Emergency at the nearest hospital, if you think that you or anyone else may have taken too much of this medicine. Do this even if there are no signs of discomfort or poisoning.

You may need urgent medical attention.

If you take too enalapril, you will may feel light-headed or dizzy, or you may faint.

While you are taking this medicine

Things you must do

Tell your doctor if you have had excessive vomiting or diarrhoea, or if you experience any of the following symptoms:

light-headedness or dizziness
dry mouth or thirst
weakness, tiredness or drowsiness
muscle pain or cramps
a fast heart beat
passing less urine than normal

If you experience these symptoms, you may be dehydrated because you are losing too much water. This is more likely to occur when you begin to take enalapril or if your dose is increased.

Make sure you drink enough water during exercise and hot weather when you are taking enalapril, especially if you sweat a lot.

If you do not drink enough water while taking enalapril, your blood pressure may drop suddenly, and you may dehydrate. If you experience any of the above symptoms, tell your doctor.

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are taking this medicine.

Tell any other doctors, dentists, and pharmacists who treat you that you are taking this medicine.

If you are going to have surgery, tell the surgeon or anaesthetist that you are taking this medicine. It may affect other medicines used during surgery.

If you become pregnant or start to breastfeed while taking this medicine, tell your doctor immediately.

If you are about to have any blood tests, tell your doctor that you are taking this medicine. It may interfere with the results of some tests.

Keep all your doctor's appointments so that your progress can be checked. Your doctor may do some tests from time to time, such as checking your blood pressure, to make sure the medicine is working and to prevent unwanted side effects.

Things you must not do

Do not take this medicine to treat any other complaints unless your doctor tells you to.

Do not give your medicine to anyone else, even if they have the same condition as you.

Do not stop taking your medicine or lower the dosage without checking with your doctor.

Things to be careful of

Be careful when driving or operating machinery until you know how this medicine affects you. Enalapril may cause dizziness or light-headedness in some people, especially after the first dose or if the dose is increased. Make sure you know how you react to enalapril before you drive a car, operate machinery, or do anything else that could be dangerous if you are dizzy or light-headed.

If you drink alcohol, the dizziness or light-headedness may be worse.

Things that would be helpful for your blood pressure or heart failure

Some self-help measures suggested below may help your condition. Talk to your doctor or pharmacist about these measures and for more information.

Alcohol – your doctor may advise you to limit your alcohol intake
Diet – eat a healthy diet which includes plenty of fresh vegetables, fruit, bread, cereals and fish. Also eat less fat and sugar
Exercise – regular exercise helps to reduce blood pressure and helps the heart get fitter, but it is important not to overdo it. Walking is a good exercise but try to find a route that is fairly flat. Before starting any exercise, ask your doctor about the best kind of programme for you.
Salt – your doctor may advise you to watch the amount of salt in your diet. To reduce your salt intake, you should avoid using salt in cooking or at the table
Smoking – your doctor may advise you to stop smoking or at least cut down
Weight – your doctor may suggest losing some weight to help lower your blood pressure and help lessen the amount of work your heart must do. Some people may need a dietician's help to lose weight

Side effects

Tell your doctor as soon as possible if you do not feel well while you are taking this medicine.

All medicines can have side effects. Sometimes they are serious but most of the time they are not. You may need medical attention if you get some of the side effects.

If you are over 65 years of age you may have an increased chance of getting side effects.

Do not be alarmed by the following lists of side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor if you notice any of the following:

light-headedness or dizziness because blood pressure is too low
headache
fatigue
dry cough
mild stomach upsets such as feeling sick, diarrhoea, or stomach pains
muscle cramps

Tell your doctor as soon as possible if you notice any of the following:

changes in the way your heart beats, e.g. if you notice it beating faster
fainting
yellowing of the skin and eyes (also called jaundice)
itchy skin rash or other skin problems
signs of worrying or frequent infections such as fever, severe chills, sore throat or mouth ulcers
passing less urine than is normal for you
signs of dehydration such as nausea, vomiting, muscle cramps, headache, drowsiness and tiredness – if untreated, mental confusion and fits may develop.
Your doctor may need to monitor your blood sodium levels.

These may be serious side effects and you may need medical attention. Mostly, these side effects are rare.

If any of the following happen, tell your doctor immediately or go to Accident and Emergency at your nearest hospital:

pinkish, itchy swellings on the skin, also called hives or nettle rash
flu-like symptoms, followed by a painful red or purplish rash on skin and mucous membranes (mouth/nose, eyelids, genitals, internal organs) that spreads and blisters
chest pain or angina
wheeziness due to tightness in the chest
collapsing, numbness or weakness of arms or legs
symptoms of an allergic reaction including cough, shortness of breath, wheezing or difficulty breathing; swelling of the face, lips, tongue, throat or other parts of the body; rash, itching or hives on the skin

These are very serious side effects and you may need urgent medical attention or hospitalisation. These side effects are usually very rare.

Tell your doctor or pharmacist if you notice anything that is making you feel unwell.

Other side effects not listed above may occur in some patients.

Some of these side effects can only be found when your doctor does tests from time to time to check your progress.

Storage and disposal

Storage

Keep your medicine in its original packaging until it is time to take it. If you take your medicine out of its original packaging it may not keep well.

Keep your medicine in a cool dry place where the temperature will stay below 25°C.

Do not store your medicine, or any other medicine, in the bathroom or near a sink. Do not leave it on a window sill or in the car. Heat and dampness can destroy some medicines.

Keep this medicine where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop taking this medicine or the expiry date has passed, ask your pharmacist what to do with any medicine that is left over.

Product description

What APO-Enalapril Tablets looks like

5 mg tablets
White to off white, round, flat-face bevelled edge tablets break line on one side and "5" debossed on the other side. AUST R 196472.

10 mg tablets
White to off white, round, flat-face bevelled edge tablets with break line on one side and "10" debossed on the other side. AUST R 196466.

20 mg tablets
White to off white, round, flat-face bevelled edge tablets with break line one side and "20" debossed on the other side. AUST R 196504.

Available in blister packs of 30.

Ingredients

Each tablet contains 5 mg, 10 mg or 20 mg of enalapril maleate as the active ingredient.

It also contains the following inactive ingredients:

maleic acid
lactose monohydrate
hypromellose
croscarmellose sodium
sodium stearylfumarate

This medicine is gluten-free, sucrose-free, tartrazine-free and free of other azo dyes.

This medicine contains sugars as lactose.

Sponsor

Arrotex Pharmaceuticals Pty Ltd
15-17 Chapel Street
Cremorne VIC
3121
Australia
www.arrotex.com.au

This leaflet was last updated in January 2024.

Published by MIMS March 2024

BRAND INFORMATION

Brand name

APO-Enalapril

Active ingredient

Enalapril maleate

Schedule

1 Name of Medicine

Enalapril maleate.

2 Qualitative and Quantitative Composition

Each tablet (5 mg, 10 mg and 20 mg) contains enalapril maleate as the active ingredient.

Excipients with known effect.

Contains sugars as lactose.
For the full list of excipients see Section 6.1 List of Excipients.

3 Pharmaceutical Form

5 mg tablets.

White to off white, round, flat-face beveled edge tablets with breakline on one side and "5" debossed on the other side.

10 mg tablets.

White to off white, round, flat-face beveled edge tablets with breakline on one side and "10" debossed on the other side.

20 mg tablets.

White to off white, round, flat-face beveled edge tablets with breakline on one side and "20" debossed on the other side.

4 Clinical Particulars

4.1 Therapeutic Indications

Enalapril is indicated in the treatment of:

Hypertension.

All grades of essential hypertension.
Renovascular hypertension.

Congestive heart failure.

All degrees of symptomatic heart failure. In such patients, it is recommended that APO-Enalapril be administered together with a diuretic.

Left ventricular dysfunction.

All degrees of left ventricular dysfunction where the left ventricular ejection fraction is less than 35%, irrespective of the presence or severity of obvious symptoms of heart failure.

4.2 Dose and Method of Administration

Essential hypertension.

In patients who are currently being treated with a diuretic, symptomatic hypotension occasionally may occur following the initial dose of APO-Enalapril. The diuretic should, if possible, be discontinued for two to three days before beginning therapy with APO-Enalapril to reduce the likelihood of hypotension (see Section 4.4 Special Warnings and Precautions for Use). If the patient's blood pressure is not controlled with APO-Enalapril alone, diuretic therapy may be resumed. If the diuretic cannot be discontinued an initial dose of 2.5 mg (break the 5 mg tablet) should be used under medical supervision for at least one hour to determine whether excess hypotension will occur (see Section 4.4 Special Warnings and Precautions for Use; Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
The recommended initial dose in patients not on diuretics is 5 mg once a day. Dosage should be adjusted according to blood pressure response. The usual dosage range is 10 to 40 mg per day administered in a single dose or two divided doses. In some patients treated once daily, the antihypertensive effect may diminish toward the end of the dosing interval. In such patients, an increase in dosage or twice daily administration should be considered. If blood pressure is not controlled with APO-Enalapril alone, a diuretic may be added.
Concomitant administration of APO-Enalapril with potassium supplements, potassium salt substitutes, or potassium-sparing diuretics may lead to increases of serum potassium (see Section 4.4 Special Warnings and Precautions for Use).
To date there is insufficient experience with APO-Enalapril in the treatment of accelerated or malignant hypertension. APO-Enalapril, therefore, is not recommended in such situations.

Dosage in the elderly (over 65 years).

The starting dose should be 2.5 mg. Some elderly patients may be more responsive to APO-Enalapril than younger patients.

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 20 mg taken once daily. For patients with hypertension who have been treated recently with diuretics, caution is recommended (see next paragraph).

Congestive heart failure.

Therapy with APO-Enalapril must be started under close medical supervision.
Blood pressure and renal function should be monitored closely both before and after starting treatment with APO-Enalapril (see Section 4.4 Special Warnings and Precautions for Use) because severe hypotension and (more rarely) consequent renal failure have been reported.
Initiation of therapy requires consideration of recent diuretic therapy and the possibility of severe salt/volume depletion. If possible, the dose of diuretic should be reduced before beginning treatment.
The initial dose of APO-Enalapril in patients with congestive heart failure (especially renally impaired or sodium- and/or volume- depleted patients) should be lower (2.5 mg or less), and it should be administered under close medical supervision to determine the initial effect on the blood pressure. The appearance of hypotension after the initial dose of APO-Enalapril does not imply that hypotension will recur during chronic therapy with APO-Enalapril and does not preclude continued use of the drug.
In the absence of, or after effective management of, symptomatic hypotension following initiation of therapy with APO-Enalapril in congestive heart failure, the dose should be gradually increased, depending on the patient's response, to the usual maintenance dose (10-20 mg) given in a single or divided dose. This dose titration may be performed over a 2 to 4 week period, or more rapidly if indicated by the presence of residual signs and symptoms of heart failure. In clinical trials in which mortality and morbidity was reduced, dosage was divided in two doses.

Left ventricular dysfunction without symptoms of overt heart failure.

In the SOLVD-Prevention trial, the initial dose was 2.5 mg twice daily and titrated, as above (see Section 4.2 Dose and Method of Administration, Congestive heart failure), to the usual maintenance dose of 20 mg in two divided doses.

Dosage adjustment in renal impairment.

The usual dose of enalapril is recommended for patients with a creatinine clearance > 30 mL/min (serum creatinine of up to approximately 3 mg/dL). For patients with creatinine clearance < 30 mL/min (serum creatinine > 3 mg/dL), the first dose is 2.5 mg once daily. The dosage may be titrated upward until blood pressure is controlled or to a maximum of 40 mg daily. See Table 1.

4.3 Contraindications

History of previous hypersensitivity to APO-Enalapril or to any component of the formulation and in patients with a history of angioneurotic oedema relating to previous treatment with an angiotensin-converting enzyme inhibitor and in patients with hereditary or idiopathic angioedema.
Pregnancy (see Section 4.6 Fertility, Pregnancy and Lactation, Use in pregnancy).
Enalapril should not be administered with aliskiren in patients with diabetes (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Enalapril is contraindicated in combination with a neprilysin inhibitor (e.g. sacubitril).
Do not administer enalapril within 36 hours of switching to or from sacubitril/valsartan, a product containing a neprilysin inhibitor. (See Section 4.4 Special Warnings and Precautions for Use; Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.)

4.4 Special Warnings and Precautions for Use

Angioedema.

Angioedema of the face, extremities, lips, tongue, glottis and/or larynx has been reported in patients treated with angiotensin converting enzyme inhibitors, including enalapril. This may occur at any time during treatment. In such cases enalapril should be promptly discontinued and the patient carefully observed until the swelling disappears. Even in those instances where swelling of only the tongue is involved, without respiratory distress, patients may require prolonged observation since treatment with antihistamines and corticosteroids may not be sufficient. Very rarely, fatalities have been reported due to angioedema associated with laryngeal oedema or tongue oedema. Patients with involvement of the tongue, glottis or larynx are likely to experience airway obstruction, especially those with a history of airway surgery.
Where there is involvement of the tongue, glottis or larynx, likely to cause airway obstruction, appropriate therapy, which may include subcutaneous adrenaline solution 1:1000 (0.3 mL to 0.5 mL) and/or measures to ensure a patent airway should be promptly administered (see Section 4.8 Adverse Effects (Undesirable Effects)).
The onset of angioedema associated with use of ACE inhibitors may be delayed for weeks or months. Patients may have multiple episodes of angioedema with long symptom-free intervals. Angioedema may occur with or without urticaria.
Black patients receiving ACE inhibitors have been reported to have higher incidence of angioedema compared to non-blacks.
Patients receiving coadministration of ACE inhibitor and mTOR (mammalian target of rapamycin) inhibitor (e.g. temsirolimus, sirolimus, everolimus) therapy may be at increased risk for angioedema.
Patients receiving concomitant ACE inhibitor and neprilysin inhibitor therapy may be at increased risk for angioedema (see Section 4.3 Contraindications; Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Patients receiving concomitant ACE inhibitor and vildagliptin may be at increased risk for angioedema (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Anaphylactoid reactions during hymenoptera desensitization.

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

Hypotension.

Excessive hypotension was rarely seen in uncomplicated hypertensive patients but is a possible consequence of enalapril use in severely salt/volume depleted persons such as those treated vigorously with diuretics or patients on dialysis or dietary salt restriction or those suffering from diarrhoea or vomiting (see Section 4.4 Special Warnings and Precautions for Use; Section 4.5 Interactions with Other Medicines and Other Forms of Interactions; Section 4.8 Adverse Effects (Undesirable Effects)). In patients with heart failure, with or without associated renal insufficiency, excessive hypotension has been observed and may be associated with oliguria and/or progressive azotaemia, and rarely with acute renal failure and/or death. Because of the potential fall in blood pressure in these patients, therapy should be started under very close medical supervision. Such patients should be followed closely for the first two weeks of treatment and whenever the dose of enalapril and/or diuretic is increased. 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 supine position and, if necessary, receive an intravenous infusion of normal saline. A transient hypotensive response is not a contraindication to further doses which usually can be given without difficulty once the blood pressure has increased after volume expansion.

Neutropenia/agranulocytosis.

Another angiotensin converting enzyme inhibitor has been shown to cause agranulocytosis and bone marrow depression (including leucopenia/neutropenia). These reports generally involve patients who have pre-existing renal dysfunction and/or collagen vascular disease, some of whom have received concomitant immunosuppressant therapy. Most reports describe transient episodes for which a causal relationship to the ACE inhibitor could not be established. Available data from clinical trials of enalapril are insufficient to show that enalapril does not cause agranulocytosis at similar rates. International marketing experience has revealed cases of neutropenia or agranulocytosis in which a causal relationship to enalapril cannot be excluded.
It is recommended that periodic haematologic monitoring be considered in patients with diseases known to affect bone marrow function (e.g. renal dysfunction, collagen vascular disease, etc.) and/or who are taking concomitant therapy known to be associated with bone marrow depression.

Use in renal impairment.

As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function may be anticipated in susceptible individuals. In patients with heart failure whose renal function may depend on the activity of the renin angiotensin aldosterone system, treatment with angiotensin converting enzyme inhibitors, including enalapril, may be associated with oliguria and/or progressive azotaemia and rarely with acute renal failure and/or death.
In clinical studies in hypertensive patients with unilateral or bilateral renal artery stenosis, increases in blood urea nitrogen and serum creatinine were observed in 20% of patients. These increases were almost always reversible upon discontinuation of enalapril and/or diuretic therapy. In such patients renal function should be monitored during the first few weeks of therapy.
Some hypertensive patients with no apparent pre-existing renal vascular disease have developed increases in blood urea and serum creatinine, usually minor and transient, especially when enalapril has been given concomitantly with a diuretic. This is more likely to occur in patients with pre-existing renal impairment. Dosage reduction of enalapril and/or discontinuation of the diuretic may be required.

Hemodialysis patients.

Anaphylactoid reactions have been reported in patients dialyzed with high-flux membranes (e.g. AN 69) 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.
Evaluation of the hypertensive patient should always include assessment of renal function (see Section 4.2 Dose and Method of Administration).

Aortic stenosis/hypertrophic cardiomyopathy.

As with all vasodilators, ACE inhibitors should be given with caution to patients with obstruction in the outflow tract of the left ventricle.

Hyperkalaemia.

(See Section 4.5 Interactions with Other Medicines and Other Forms of Interactions, Agents increasing serum potassium).
Elevated serum potassium (greater than 5.7 mmol/L) was observed in approximately one percent of hypertensive patients in clinical trials. In most cases these were isolated values which resolved despite continued therapy. Hyperkalaemia was a cause of discontinuation of therapy in 0.28 percent of hypertensive patients. Risk factors for the development of hyperkalaemia may include renal insufficiency, diabetes mellitus, and the concomitant use of potassium-sparing diuretics (e.g. spironolactone, eplerenone, triamterene, or amiloride), potassium supplements, potassium-containing salt substitutes, or other drugs that may increase serum potassium (e.g. trimethoprim-containing products), which should be used cautiously, if at all, with enalapril.
The use of potassium supplements, potassium-sparing diuretics, potassium-containing salt substitutes, or other drugs that may increase serum potassium, particularly in patients with impaired renal function may lead to a significant increase in serum potassium. Hyperkalaemia can cause serious, sometimes fatal, arrhythmias.
If concomitant use of enalapril and any of the above-mentioned agents is deemed appropriate, they should be used with caution and with frequent monitoring of serum potassium.

Hypoglycaemia.

Diabetic patients treated with oral anti-diabetic agents or insulin starting an ACE inhibitor should be told to closely monitor for hypoglycaemia, especially during the first month of combined use (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions, Anti-diabetics).

Surgery/anaesthesia.

In patients undergoing major surgery or during anaesthesia with agents that produce hypotension, enalapril may block 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.

Cough.

A persistent non-productive, ticklish cough has been reported in some patients undergoing treatment with enalapril and other ACE inhibiting drugs. The cough is often worse when lying down. The cough is more common in women (who account for about two thirds of reported cases). The patients who cough may have increased bronchial reactivity compared to those who do not cough. It may disappear in some patients with continued use, or diminish or disappear if the dose of the drug is reduced. In those in whom cough persists, the drug should be discontinued. The cough usually returns on rechallenge. No residual effects have been reported.

Use in the elderly.

See Section 4.5 Interactions with Other Medicines and Other Forms of Interactions; Section 4.2 Dose and Method of Administration.

Paediatric use.

Enalapril has not been studied in children.

Effects on laboratory tests.

No data available.

Laboratory test findings.

Serum electrolytes.

Hyperkalaemia (see Section 4.4 Special Warnings and Precautions for Use, Hyperkalaemia), hyponatraemia.

Creatinine, blood urea nitrogen.

In controlled clinical trials minor increases in blood urea nitrogen and serum creatinine, reversible upon discontinuation of therapy, were observed in about 0.2 percent of patients with essential hypertension treated with enalapril alone. Increases are more likely to occur in patients receiving concomitant diuretics or in patients with renal artery stenosis (see Section 4.4 Special Warnings and Precautions for Use).

Haemoglobin and haematocrit.

Small decreases in haemoglobin and haematocrit (mean decreases of approximately 0.3 g percent and 1.0 vol percent, respectively) occur frequently in hypertensive patients treated with enalapril but are rarely of clinical importance unless another cause of anaemia coexists. In clinical trials, less than 0.1 percent of patients discontinued therapy due to anaemia.

Other (causal relationship unknown).

In marketing experience, rare cases of pancreatitis, neutropenia, thrombocytopenia, agranulocytosis and bone marrow depression have been reported. A few cases of haemolysis have been reported in patients with G6PD deficiency.

Liver function tests.

Elevations of liver enzymes and/or serum bilirubin have occurred.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Hypotension-patients on diuretic therapy.

Patients on diuretics and especially those in whom diuretic therapy was recently instituted, may occasionally experience an excessive reduction of blood pressure after initiation of therapy with enalapril. The possibility of hypotensive effects with enalapril can be minimised by either discontinuing the diuretic or increasing the salt intake prior to initiation of treatment with enalapril. If it is necessary to continue the diuretic, provide medical supervision for at least one hour after the initial dose (see Section 4.4 Special Warnings and Precautions for Use; Section 4.2 Dose and Method of Administration).

Agents causing renin release.

The antihypertensive effect of enalapril is augmented by antihypertensive agents that cause renin release (e.g. diuretics).

Other cardiovascular agents.

Enalapril has been used concomitantly with beta adrenergic-blocking agents, methyldopa, nitrates, calcium-blocking agents, hydralazine and prazosin without evidence of clinically significant adverse interactions.

Agents increasing serum potassium.

(See Section 4.4 Special Warnings and Precautions for Use, Hyperkalaemia). Enalapril may attenuate potassium loss caused by thiazide-type diuretics. Risk factors for the development of hyperkalaemia include renal insufficiency and diabetes mellitus and concomitant use of potassium-sparing diuretics (e.g. spironolactone, eplerenone, triamterene, or amiloride), potassium supplements, potassium-containing salt substitutes, or other drugs that may increase serum potassium (e.g. trimethoprim-containing products), which may lead to significant increases in serum potassium. If concomitant use of enalapril with potassium-sparing diuretics, potassium supplements, or potassium containing salt substitutes is indicated because of demonstrated hypokalaemia, they should be used with caution and with frequent monitoring of serum potassium.

Anti-diabetics.

Epidemiological studies have suggested that concomitant administration of ACE inhibitors and anti-diabetic medicines (insulins, oral hypoglycaemic agents) may cause an increased blood-glucose-lowering effect with risk of hypoglycaemia. This phenomenon appeared to be more likely to occur during the first weeks of combined treatment and in patients with renal impairment. In diabetic patients treated with oral anti-diabetic agents or insulin, glycaemic control should be closely monitored for hypoglycaemia, especially during the first month of treatment with an ACE inhibitor.

Serum lithium.

As with other drugs which eliminate sodium, lithium clearance may be reduced. Therefore, the serum lithium levels should be monitored carefully if lithium salts are to be administered.

Non-steroidal anti-inflammatory drugs including selective cyclooxygenase-2 inhibitors.

Non-steroidal anti-inflammatory drugs (NSAIDs) including selective cyclooxygenase-2 inhibitors (COX-2 inhibitors) may reduce the effect of diuretics and other antihypertensive drugs. Therefore, the antihypertensive effect of angiotensin II receptor antagonists or ACE inhibitors may be attenuated by NSAIDs including selective COX-2 inhibitors.
In some patients with compromised renal function (e.g. elderly patients or patients who are volume-depleted, including those on diuretic therapy) who are being treated with non-steroidal anti-inflammatory drugs including selective cyclooxygenase-2 inhibitors, the co-administration of angiotensin II receptor antagonists or ACE inhibitors may result in a further deterioration of renal function, including possible renal failure. These effects are usually reversible. Therefore, the combination should be administered with caution in patients with compromised renal function.
These interactions should be considered in patients taking NSAIDs including selective COX-2 inhibitors concomitantly with diuretics and ACE inhibitors. Therefore, the combination should be administered with caution, especially in the elderly.

Combination use of ACE inhibitors or angiotensin receptor antagonists, anti-inflammatory drugs and thiazide diuretics.

The use of an ACE inhibiting drug (ACE inhibitor or angiotensin receptor antagonist), an anti-inflammatory drug (NSAID or COX-2 inhibitor) and a thiazide diuretic at the same time increases the risk of renal impairment. This includes use in fixed-combination products containing more than one class of drug. Combined use of these medications should be accompanied by increased monitoring of serum creatinine, particularly at the institution of the combination. The combination of drugs from these three classes should be used with caution particularly in elderly patients or those with pre-existing renal impairment.

Dual blockade of the renin-angiotensin-aldosterone system.

Dual blockade of the renin-angiotensin-aldosterone system (RAAS) with angiotensin receptor blockers, ACE inhibitors, or direct renin inhibitors (such as aliskiren) is associated with increased risks of hypotension, syncope, hyperkalaemia, and changes in renal function (including acute renal failure) compared to monotherapy. Closely monitor blood pressure, renal function, and electrolytes in patients on enalapril and other agents that affect the RAAS. Do not co-administer aliskiren with enalapril in patients with diabetes. Avoid use of aliskiren with enalapril in patients with renal impairment (GFR < 60 mL/min).

Gold.

Nitritoid reactions (symptoms include facial flushing, nausea, vomiting and hypotension) have been reported rarely in patients on therapy with injectable gold (sodium aurothiomalate) and concomitant ACE inhibitor therapy including enalapril.

Mammalian target of rapamycin (mTOR) inhibitors.

Patients taking concomitant mTOR inhibitor (e.g. temsirolimus, sirolimus, everolimus) therapy may be at increased risk for angioedema (see Section 4.4 Special Warnings and Precautions for Use).

Neprilysin inhibitors.

Patients taking a concomitant neprilysin inhibitor (e.g. sacubitril) may be at increased risk for angioedema (see Section 4.3 Contraindications; Section 4.4 Special Warnings and Precautions for Use).

Vildagliptin.

Patients taking concomitant vildagliptin may be at increased risk for angioedema (see Section 4.4 Special Warnings and Precautions for Use).

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category D)
As with all ACE inhibitors, enalapril should not be taken during pregnancy. Pregnancy should be excluded before starting treatment with enalapril and avoided during treatment.
If a patient intends to become pregnant, treatment with ACE inhibitors must be discontinued and replaced by another form of treatment. If a patient becomes pregnant while on ACE inhibitors, she must immediately inform her doctor to discuss a change in medication and further management.
There are no adequate and well-controlled studies of enalapril in pregnant women. Data, however, show that enalapril crosses the human placenta. Post marketing experience with all ACE inhibitors suggest that exposure in utero may be associated with hypotension and decreased renal perfusion in the foetus. ACE inhibitors have also been associated with foetal death in utero. There have been reports of foetal hypotension, renal failure, hyperkalaemia, skull hypoplasia and death when ACE inhibitors have been used during the second and third trimesters of pregnancy.
A historical cohort study in over 29,000 infants born to non-diabetic mothers has shown 2.7 times higher risk for congenital malformations in infants exposed to any ACE inhibitor during the first trimester compared to no exposure. The risk ratios for cardiovascular and central nervous system malformations were 3.7 times (95% confidence interval 1.89 to 7.3) and 4.4 times (95% confidence interval 1.37 to 14.02) respectively compared to no exposure.
There is a potential risk of foetal hypotension, decreased birth weight and decreased renal perfusion or anuria in the foetus from in utero exposure to ACE inhibitors. Oligohydramnios in the mother has also been reported, presumably representing decreased renal function in the foetus and may result in limb contractures, craniofacial deformations and hypoplastic lung development. Any neonate exposed to enalapril in utero should be observed closely for adequate urine output, blood pressure and hyperkalaemia. If required, appropriate medical measures should be initiated including administration of fluids or dialysis to remove enalaprilat from the circulatory system.
The maternal and foetal toxicity occurred in some rabbits at doses of 1 mg/kg/day or more. Saline supplementation prevented the maternal and foetal toxicity seen at doses of 3 and 10 mg/kg/day, but not at 30 mg/kg/day. Enalapril was not teratogenic in rabbits. There was no foetotoxicity of teratogenicity in rats treated with up to 200 mg/kg/day of enalapril. Foetotoxicity expressed as a decrease in average foetal weight occurred in rats given 1200 mg/kg/day of enalapril, but did not occur when these animals were supplemented with saline.
It is not known if enalapril is secreted in human milk. However, enalapril has been demonstrated to be secreted into the milk of lactating rats. In view of this and a lack of knowledge of the effects of enalapril on neonates, this product should not be used during lactation or else breast feeding should be discontinued.

4.7 Effects on Ability to Drive and Use Machines

When driving vehicles or operating machines it should be taken into account that occasionally dizziness or weariness may occur. (See Section 4.8 Adverse Effects (Undesirable Effects)).

4.8 Adverse Effects (Undesirable Effects)

Enalapril has been evaluated for safety in more than 10,000 patients, including over 1000 patients treated for one year or more. Enalapril has been found to be generally well tolerated in controlled clinical trials involving 2677 patients.
The most frequent clinical adverse experiences in controlled trials were: headache (4.8%), dizziness (4.6%) and fatigue (2.8%). For the most part, adverse experiences were mild and transient in nature. Discontinuation of therapy was required in 6% of patients. In clinical trials, the overall frequency of adverse experiences was not related to total daily dosage within the range of 10 to 40 mg. The overall percentage of patients treated with enalapril reporting adverse experiences was comparable to placebo. Adverse experiences occurring in greater than 1% of patients treated with enalapril in controlled clinical trials are shown in Table 2.
Clinical adverse experiences occurring since the drug was marketed or in 0.5 to 1.0% of patients in the controlled trials are listed below and, within each category, are in order of decreasing severity.

Cardiovascular.

Myocardial infarction or cerebrovascular accident, possibly secondary to excessive hypotension in high risk patients (see Section 4.4 Special Warnings and Precautions for Use, Hypotension), syncope, orthostatic hypotension, palpitations, chest pain, rhythm disturbances, angina pectoris, Raynaud's phenomenon.

Endocrine.

Syndrome of inappropriate antidiuretic hormone secretion (SIADH).

Gastrointestinal system.

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

Metabolic.

Cases of hypoglycaemia in diabetic patients on oral antidiabetic agents or insulin have been reported (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Nervous system/psychiatric.

Depression, confusion, somnolence, insomnia, nervousness, paraesthesia, vertigo, dream abnormality.

Renal.

Renal failure, oliguria, renal dysfunction (see Section 4.4 Special Warnings and Precautions for Use; Section 4.2 Dose and Method of Administration).

Respiratory.

Pulmonary infiltrates, bronchospasm/asthma, dyspnoea, rhinorrhoea, sore throat and hoarseness.

Skin.

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

Other.

Vasculitis, muscle cramps, hyperhidrosis, impotence, asthenia, photosensitivity, flushing, taste alteration, tinnitus, glossitis, blurred vision.
A symptom complex has been reported which may include fever, serositis, myalgia and arthralgia/arthritis; an elevated ESR, a positive ANA, eosinophilia and leukocytosis. Rash, photosensitivity or other dermatological manifestations may occur. These symptoms have disappeared after discontinuation of therapy.

Angioedema.

Angioedema has been reported in patients receiving enalapril (0.2 percent). Angioedema associated with laryngeal oedema may be fatal. If angioedema of the face, extremities, lips, tongue, glottis and/or larynx occurs, treatment with enalapril should be discontinued and appropriate therapy instituted immediately (see Section 4.4 Special Warnings and Precautions for Use). In very rare cases, intestinal angioedema has been reported with angiotensin converting enzyme inhibitors including enalapril.

Hypotension.

Combining the results of clinical trials in patients with hypertension or congestive heart failure, hypotension (including postural hypotension, and other orthostatic effect) was reported in 2.3 percent of patients following the initial dose of enalapril or during extended therapy. In the hypertensive patients, hypotension occurred in 0.9 percent and syncope occurred in 0.5 percent of patients. Hypotension or syncope was a cause for discontinuation of therapy in 0.1 percent of hypertensive patients. (See Section 4.4 Special Warnings and Precautions for Use).

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration 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 at www.tga.gov.au/reporting-problems.

4.9 Overdose

Symptoms.

Limited data are available with regard to overdosage in humans. The most likely manifestation of overdosage would be hypotension, beginning approximately six hours after ingestion of tablets, concomitant with blockade of the renin angiotensin system, and stupor, which can be treated, if necessary, by intravenous infusion of normal saline solution. Several hypertensive patients in clinical studies have received as much as 80 mg of enalaprilat intravenously over a fifteen minute period. No adverse effects, other than those associated with recommended dosages, were observed.

Treatment.

Enalaprilat may be removed from the general circulation by haemodialysis.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Enalapril maleate is a pro-drug which when administered orally is hydrolysed to release the active converting enzyme inhibitor enalaprilat. The liver appears to be the main site for this conversion.
How enalapril, or converting enzyme inhibitors in general, lower blood pressure is not entirely clear. The mechanism most favoured is inhibition of the angiotensin converting enzyme (ACE), a peptidyl dipeptidase which catalyses the conversion of angiotensin I to the pressor substance angiotensin II. Inhibition of ACE results in decreased plasma angiotensin II, which leads to increased plasma renin activity (due to removal of negative feedback of renin release), and decreased aldosterone secretion.
While the mechanism through which enalapril lowers blood pressure is believed to be primarily suppression of the renin-angiotensin-aldosterone system, which plays a major role in the regulation of blood pressure, enalapril is antihypertensive even in patients with low renin hypertension. Enalapril may also block the degradation of bradykinin, a potent vasodepressor peptide; however, the role that this plays in the therapeutic effect of enalapril remains to be elucidated.
Administration of enalapril to patients with hypertension results in a reduction of both supine and standing blood pressure without a significant increase in heart rate. Symptomatic postural hypotension is infrequent. In some patients the development of optimal blood pressure reduction may require several weeks of therapy. Abrupt withdrawal of enalapril has not been associated with rapid increase in blood pressure.
Effective inhibition of ACE activity usually occurs 2 to 4 hours after oral administration of an individual dose of enalapril. Onset of antihypertensive activity was usually seen at one hour, with peak reduction of blood pressure achieved by 4 to 6 hours after administration.
The duration of effect is dose-related. However, at recommended doses, antihypertensive and haemodynamic effects have been shown to be maintained for at least 24 hours.
In haemodynamic studies in patients with essential hypertension, blood pressure reduction was accompanied by a reduction in peripheral arterial resistance with an increase in cardiac output and little or no change in heart rate. Following administration of enalapril there was an increase or no change in renal blood flow; glomerular filtration rate was unchanged. However, in patients with low pre-treatment glomerular filtration rates, the rates were usually increased.
When given together with thiazide-type diuretics, the blood pressure lowering effects of enalapril are at least additive enalapril may reduce or prevent the development of thiazide induced hypokalaemia.
In patients with heart failure on therapy with digitalis and diuretics, treatment with oral or parenteral enalapril was associated with decreases in peripheral resistance and blood pressure. Cardiac output increased, while heart rate (usually elevated in patients with heart failure) decreased. Pulmonary capillary wedge pressure was also reduced. Exercise tolerance and severity of heart failure, as measured by New York Heart Association criteria, improved. These actions continued during chronic therapy.

Clinical trials.

In a multicentre, placebo-controlled clinical trial (SOLVD), 2569 patients with all degrees of symptomatic heart failure and ejection fraction ≤ 35% enalapril and followed for up to 55 months (SOLVD-Treatment).
A second multicentre trial used the SOLVD protocol for a study of patients with minimal or no symptoms of heart failure. SOLVD-Prevention patients, who had left ventricular ejection fraction (n = 2117) or enalapril (n = 2111) and followed for up to 5 years. These patients had little or no limitation of exercise tolerance due to dyspnoea or fatigue at randomisation and did not require treatment with digitalis, diuretics or vasodilators for heart failure at entry into the trial. The majority of patients in the trial had a history of ischaemic heart disease. A history of myocardial infarction was present in 80% of patients, current angina pectoris in 34% and a history of hypertension in 37%. Patients who had a recent myocardial infarction (i.e. Within the preceding 30 days) were not included in the SOLVD trials.
In patients with left ventricular ejection fractions of less than 35%, enalapril has been shown to retard the progression of heart failure, reduce hospitalisations for heart failure and reduce the risk of myocardial infarction. In addition, in patients who have significant symptoms of heart failure (New York Heart Association Classes 2-4) and also left ventricular ejection fractions of less than 35%, enalapril has been shown to improve survival and reduce hospitalisations for unstable angina pectoris.

5.2 Pharmacokinetic Properties

Absorption and distribution.

Oral enalapril is rapidly absorbed, with peak serum concentrations of enalapril occurring within one hour. Based on urinary recovery, the extent of absorption of enalapril from oral enalapril is approximately 60%. The oral bioavailability of enalaprilat is approximately 40%. Protein binding is approximately 50%.
The absorption of oral enalapril is not influenced by the presence of food in the gastrointestinal tract. The extent of absorption and hydrolysis of enalapril are similar for the various doses in the recommended therapeutic range.

Metabolism.

Following absorption, oral enalapril is rapidly and extensively hydrolyzed to enalaprilat, a potent angiotensin converting enzyme inhibitor. Peak serum concentrations of enalaprilat occur 3 to 4 hours after an oral dose of enalapril.

Excretion.

Excretion of enalaprilat is primarily renal. The principal components in urine are enalaprilat, accounting for about 40% of the dose, and intact enalapril. Except for conversion to enalaprilat, there is no evidence for significant metabolism of enalapril. The serum concentration profile of enalaprilat exhibits a prolonged terminal phase, apparently associated with binding to angiotensin converting enzyme (ACE).
In subjects with normal renal function, steady-state serum concentrations of enalaprilat were achieved by the fourth day of administration of enalapril. The plasma concentration time profile of enalaprilat was complex with several exponentials including a very prolonged terminal phase (t_1/2 > 30 hr). The effective half-life for accumulation of enalaprilat following multiple doses of oral enalapril is 11 hours.

5.3 Preclinical Safety Data

Genotoxicity.

Neither enalapril maleate nor the active diacid was mutagenic in the Ames microbial mutagen test with or without metabolic activation. Enalapril was also negative in the following genotoxicity studies: rec-assay, reverse mutation assay with E. coli, sister chromatid exchange with cultured mammalian cells, and the micronucleus test with mice, as well as in an in vivo cytogenic study using mouse bone marrow.
There were no adverse effects on reproductive performance in male and female rats treated with 10 to 90 mg/kg/day of enalapril.

Carcinogenicity.

There was no evidence of a carcinogenic effect when enalapril was administered for 106 weeks to rats at doses up to 90 mg/kg/day. Enalapril has also been administered for 94 weeks to male and female mice at doses up to 90 mg and 180 mg/kg/day, respectively, and showed no evidence of carcinogenicity.

6 Pharmaceutical Particulars

6.1 List of Excipients

Maleic acid, lactose monohydrate, hypromellose, croscarmellose sodium, sodium stearylfumarate.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine, see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C. Protect from light and moisture.

6.5 Nature and Contents of Container

APO-Enalapril 5 mg tablets.

Tablets are packaged in blister packs (PVC/PVDC/Al) of 30.

APO-Enalapril 10 mg tablets.

Tablets are packaged in blister packs (PVC/PVDC/Al) of 30.

APO-Enalapril 20 mg tablets.

Tablets are packaged in blister packs (PVC/PVDC/Al) of 30.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

APO-Enalapril Tablets contain the maleate salt of enalapril, the ethyl ester of the parent diacid, enalaprilat. Enalapril (enalapril maleate) is the maleate salt of enalapril, a derivative of two amino acids, L-alanine and L-proline. Following oral administration, enalapril is rapidly absorbed and then hydrolysed to enalaprilat, which is a specific, long-acting, angiotensin converting enzyme inhibitor.
Enalapril maleate is a white or almost white crystalline powder with a melting point of about 144°C and a pKa of 3 and 5.4. It is sparingly soluble in water, freely soluble in methanol, practically insoluble in methylene chloride. It dissolves in dilute solutions of alkali hydroxides.

Chemical structure.

Chemical name: (2S)-1-[(2S)-2- [[(1S)-1-(Ethoxycarbonyl)-3-phenylpropyl] amino]propanoyl] pyrrolidine-2-carboxylic acid, (Z)-2- butenedioate salt (1:1).
Molecular formula: C₂₀H₂₈N₂O₅.C₄H₄O₄.
Molecular weight: 492.5.

CAS number.

76095-16-4.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

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APO-Enalapril 10 mg Tablets

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