Consumer medicine information

Renitec [8975]

Enalapril maleate

BRAND INFORMATION

Brand name

Renitec M Tablets

Active ingredient

Enalapril maleate

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Renitec [8975].

What is in this leaflet

This leaflet answers some common questions about RENITEC. 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 RENITEC 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 RENITEC is used for

RENITEC lowers high blood pressure, which doctors call hypertension. It is also used to treat heart failure.

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. RENITEC helps to lower your blood pressure.

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 activity such as walking. Some patients may wake up short of breath at night. Fluid may collect in different parts of the body, often first noticed as swollen ankles and feet.

RENITEC helps to treat heart failure, whether you have symptoms or not. In many patients with heart failure who have symptoms, RENITEC may slow the progression of heart failure and reduce the need to go to hospital as a result of heart failure. RENITEC may help some of these patients live longer.

In many patients with heart failure who have no symptoms, RENITEC may help to stop the heart muscle from getting weaker. RENITEC 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. These patients may be less likely to have hospital stays due to heart failure.

By taking RENITEC, heart failure patients may have less chance of having a heart attack.

When used to treat heart failure, RENITEC is almost always used with other medicines called diuretics or fluid tablets. These medicines help the kidney get rid of excess fluid from the body.

How RENITEC works

One of the ways RENITEC 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.

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

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

RENITEC is not addictive.

Before you take RENITEC

When you must not take it

Do not take RENITEC if:

  • you have taken any other 'ACE inhibitor' medicines for high blood pressure or heart failure before, which caused your face, lips, tongue, throat, hands or feet to swell up, or made it hard for you to breathe
    If you have had an allergic reaction to an ACE inhibitor before, you may be allergic to RENITEC.
  • you have an allergy to RENITEC, Amprace® or other brands of enalapril maleate, or any of the ingredients listed at the end of this leaflet
    Symptoms of an allergic reaction to RENITEC or other brands of enalapril maleate may include skin rash, itchiness, shortness of breath, swelling of the face, lips or tongue, muscle pain or tenderness or joint pain.
  • you have a history of swelling of the face, lips, tongue, throat, hands or feet, for no apparent reason.
  • you have diabetes and are taking a medicine called aliskiren to reduce blood pressure.
  • you are taking a medicine containing a neprilysin inhibitor (e.g., sacubitril). Do not take RENITEC for at least 36 hours before or after you take sacubitril/valsartan, a medicine containing a neprilysin inhibitor.

Do not take RENITEC if you are pregnant or breast-feeding.

Your baby may absorb this medicine in the womb or from breast milk and therefore there is a possibility of harm to the baby.

Do not take RENITEC if:

  • the packaging is torn or shows signs of tampering
  • the expiry date on the pack has passed.
    If you take this medicine after the expiry date has passed, it may not work.

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

Before you start to take it

Tell your doctor if:

  1. you are or intend to become pregnant or intend to breast-feed

RENITEC should not be used during pregnancy or while breast-feeding.


  1. you have any medical conditions, especially the following:
  • kidney disease, or are undergoing dialysis
  • diabetes
  • heart problems
  1. you have recently suffered from excessive vomiting or diarrhoea
  2. you are following a very low salt diet
  3. you have had an allergy to any other medicines or any other substances, such as foods, preservatives or dyes.
  4. if you suffer from low blood pressure (you may notice this as faintness or dizziness, especially when standing).
  5. surgery and anaesthesia (even at the dentist office) are scheduled, as there may be a sudden fall in blood pressure associated with anaesthesia.
  6. you are taking a medicine containing a neprilysin inhibitor (e.g., sacubitril).

If you have not told your doctor about any of the above, tell them before you take any RENITEC.

Taking other medicines

Tell your doctor if you are taking any other medicines, including medicines that you buy without a prescription from your pharmacy, supermarket or health food shop. Some medicines and RENITEC may interfere with each other. These include:

  • other blood pressure medicines
  • diuretic tablets - also called fluid or water tablets
  • lithium, a medicine used to treat mood swings and some types of depression
  • potassium tablets
  • potassium-containing salt substitutes
  • potassium-sparing agents (e.g. spironolactone, eplerenone, triamterene, amiloride)
  • non-steroidal anti-inflammatory medicines (NSAIDs or Coxibs/COX-2 inhibitors), used to relieve pain, swelling and other symptoms of inflammation
  • arthritis medicines including gold therapy
  • insulin or oral antidiabetic medicines. You should be closely monitored for low blood glucose levels, especially during the first month of treatment with RENITEC.
  • mammalian target of rapamycin inhibitors (e.g. temsirolimus, sirolimus, everolimus) or a medicine containing a neprilysin inhibitor (e.g., sacubitril).

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

Your doctor or pharmacist has more information on medicines to avoid while taking RENITEC.

How to take RENITEC

How much to take

Your doctor will tell you how many tablets you need to take each day. This depends on your condition and whether you are taking other medicines. Take RENITEC only when prescribed by your doctor.

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.

Follow all directions given to you by your doctor carefully.

They may differ from the information contained in this leaflet.

If you do not understand the instructions on the box, ask your doctor or pharmacist for help.

How to take it

Take your RENITEC at about the same time each day.

Taking your tablet(s) at the same time each day will have the best effect. It will also help you remember when to take the tablets.

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

Swallow RENITEC with a glass of water.

How long to take it

RENITEC helps control your high blood pressure and helps improve your heart failure, but does not cure it. Therefore RENITEC must be taken every day. Continue taking RENITEC for as long as your doctor prescribes.

If you forget to take it

If it is almost time for 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 tablet(s) as you would normally.

If you are not sure whether to skip the dose, talk to your doctor or pharmacist.

Do not take a double dose to make up for the dose that you missed.

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

If you take too much (overdose)

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

If you take too many tablets, you will probably feel light-headed or dizzy, or you may faint.

While you are using RENITEC

Things you must do

Have your blood pressure checked when your doctor says, to make sure RENITEC is working.

If you feel any light-headedness or dizziness after you take your first dose of RENITEC or if your dose is increased, tell your doctor immediately. This is especially important if you are taking RENITEC for heart failure.

If you feel light-headed, dizzy or faint, get up slowly when getting out of bed or standing up.

You may feel light-headed or dizzy, especially if you are also taking a diuretic (fluid tablet). This may be because your blood pressure is falling suddenly. Standing up slowly, especially when you get up from bed or chairs, will help your body get used to the change in position and blood pressure. If this problem gets worse or continues, talk to your doctor.

If you become pregnant while taking RENITEC, tell your doctor immediately.

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

If you plan to have surgery (even at the dentist) that needs a general anaesthetic, tell your doctor or dentist that you are taking RENITEC.

Your blood pressure may drop suddenly.

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

If you do not drink enough water while taking RENITEC, you may faint or feel light-headed or sick. This is because your blood pressure is dropping suddenly. If you continue to feel unwell, tell your doctor.

If you have excessive vomiting and/or diarrhoea while taking RENITEC, tell your doctor.

This can also mean that you are losing too much water and salt, and may drop your blood pressure too much.

Go to your doctor regularly for a check-up.

Your doctor may occasionally do a blood test to check your potassium level in the blood and to see how your kidneys are working.

Things you must not do

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

Things to be careful of

Be careful driving or operating machinery until you know how RENITEC affects you.

RENITEC 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 RENITEC 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, 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 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 has to do. Some people may need a dietician's help to lose weight.

Side Effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking RENITEC.

RENITEC helps most people with high blood pressure and heart failure, but it may have unwanted side effects in a few people. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

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

Tell your doctor if you notice any of the following and they worry you:

  • 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

These are usually mild side effects of RENITEC, but may be serious.

Tell your doctor immediately if you notice any of the following:

  • changes in the way your heart beats, for example, 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. You may need urgent medical attention.

Serious side effects are rare.

If any of the following happen, stop taking RENITEC and tell your doctor immediately or go to accident and emergency at your nearest hospital:

  • swelling of the face, lips, mouth or throat which may cause difficulty in swallowing or breathing
  • swelling of the hands, feet, or ankles
  • pinkish, itchy swellings on the skin, also called hives or nettlerash
  • chest pain, angina
  • wheeziness due to tightness in the chest
  • collapse, numbness or weakness of arms or legs

These are serious side effects. You may need urgent medical attention or hospitalisation.

All of these side effects are rare.

Other side effects not listed above may also occur in some patients. Tell your doctor if you notice any other effects.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

After using RENITEC

Storage

Keep your tablets in the blister pack until it is time to take them.

If you take the tablets out of the blister pack and store them in another container they will not keep well and they may become soft and crumbly.

RENITEC Tablets should be kept in a cool dry place where the temperature stays below 25°C.

Do not store it or any other medicine in the bathroom or near a sink.

Do not leave it in the car or on window sills.

Heat and dampness can destroy some medicines.

Keep it 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 RENITEC or the tablets have passed their expiry date, ask your pharmacist what to do with any that are left over.

Product description

What it looks like

RENITEC comes in three types of tablets:

  • RENITEC M - white, barrel-shaped tablet with RENITEC marked on one side and scored on the other side.
  • RENITEC - rust-red, barrel-shaped tablet with RENITEC marked on one side and scored on the other side.
  • RENITEC 20 - peach coloured, barrel-shaped tablet with MSD714 marked on one side.

A box of RENITEC contains 30 tablets.

Ingredients

Active ingredient:

  • RENITEC M - 5 mg enalapril maleate per tablet
  • RENITEC - 10 mg enalapril maleate per tablet
  • RENITEC 20 - 20 mg enalapril maleate per tablet

Inactive ingredients:

  • Lactose monohydrate
  • sodium bicarbonate
  • maize starch
  • pregelatinised maize starch
  • magnesium stearate
  • iron oxide red (RENITEC 10 mg and RENITEC 20 mg)
  • iron oxide yellow (RENITEC 20 mg)

RENITEC does not contain gluten, sucrose, tartrazine or any other azo dyes.

Manufacturer/Supplier

RENITEC is supplied in Australia by:

Merck Sharp & Dohme (Australia) Pty Limited
Level 1 Building A, 26 Talavera Road, Macquarie Park NSW 2113

Based on Product Information approved 25 January 2018.

Australian Register Numbers:

RENITEC M - AUST R 10514

RENITEC - AUST R 10521

RENITEC 20 - AUST R 10515

BRAND INFORMATION

Brand name

Renitec M Tablets

Active ingredient

Enalapril maleate

Schedule

S4

 

1 Name of Medicine

Enalapril maleate.

6.7 Physicochemical Properties

Renitec (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.
Renitec tablets contain the maleate salt of enalapril, the ethyl ester of the parent diacid, enalaprilat. Enalapril maleate is chemically described as (S)-1-[N-[1-(ethoxycarbonyl)-3-phenylpropyl]-L-alanyl]-L-proline, (Z)-2-butenedioate salt (1:1). It lacks a sulphydryl group. Its empirical formula is C20H28N2O5.C4H4O4. It has a molecular weight of 492.53.

Chemical structure.


CAS number.

76095-16-4.

2 Qualitative and Quantitative Composition

Enalapril maleate is a white to off white crystalline powder. It is sparingly soluble in water, soluble in ethanol, and freely soluble in methanol and dimethylformamide.
Renitec tablets contain 5 mg, 10 mg or 20 mg enalapril maleate.
List of excipients with known effect: lactose monohydrate.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Renitec M (enalapril maleate) 5 mg, white, barrel shaped biconvex compressed tablet, scored on one side and engraved 'Renitec' on the other.
Renitec (enalapril maleate) 10 mg, rust red, barrel shaped biconvex compressed tablet, scored on one side and engraved 'Renitec' on the other.
Renitec 20 (enalapril maleate) 20 mg, peach barrel shaped biconvex compressed tablet engraved 'MSD714' on one side.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Enalapril maleate is a prodrug 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.
Administration of Renitec 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 Renitec 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 Renitec there was an increase or no change in renal blood flow; glomerular filtration rate was unchanged. However, in patients with low pretreatment glomerular filtration rates, the rates were usually increased.
When given together with thiazide type diuretics, the blood pressure lowering effects of Renitec are at least additive. Renitec 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 Renitec 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.

Mechanism of action.

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 Renitec 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, Renitec is antihypertensive even in patients with low renin hypertension. Renitec may also block the degradation of bradykinin, a potent vasodepressor peptide; however, the role that this plays in the therapeutic effect of Renitec remains to be elucidated.

Clinical trials.

In a multicentre, placebo controlled clinical trial (SOLVD), 2,569 patients with all degrees of symptomatic heart failure and ejection fraction ≤ 35% were randomised to placebo or 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 ≤ 35% and no history of symptomatic heart failure were randomised to placebo (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%, Renitec 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%, Renitec 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 Renitec is approximately 60%. The oral bioavailability of enalaprilat is approximately 40%. Protein binding is approximately 50%.
The absorption of oral Renitec 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 Renitec.

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 Renitec. 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 Renitec. The plasma concentration time profile of enalaprilat was complex with several exponentials including a very prolonged terminal phase (t1/2 > 30 hr). The effective half life for accumulation of enalaprilat following multiple doses of oral Renitec 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.

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.

4 Clinical Particulars

4.1 Therapeutic Indications

Hypertension.

Renitec is indicated in the treatment of:
all grades of essential hypertension;
renovascular hypertension.

Congestive heart failure.

Renitec is indicated for the treatment of all degrees of symptomatic heart failure. In such patients it is recommended that Renitec 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.

4.3 Contraindications

1. History of previous hypersensitivity to Renitec 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.
2. Pregnancy (see Section 4.6 Fertility, Pregnancy and Lactation, Use in pregnancy).
3. Renitec should not be administered with aliskiren in patients with diabetes (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
4. Renitec is contraindicated in combination with a neprilysin inhibitor (e.g. sacubitril). Do not administer Renitec 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

General.

Angioedema.

Angioedema of the face, extremities, lips, tongue, glottis and/or larynx has been reported in patients treated with angiotensin converting enzyme inhibitors, including Renitec. This may occur at any time during treatment. In such cases Renitec 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 nonblacks.
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).

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.

Haemodialysis 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 Renitec.
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 Renitec 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 antidiabetic 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, Antidiabetics.)

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 nonproductive, 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 commoner 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 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 Renitec, 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 percent 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 Renitec has been given concomitantly with a diuretic. This is more likely to occur in patients with pre-existing renal impairment. Dosage reduction of Renitec and/or discontinuation of the diuretic may be required.

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.

Renitec 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 Renitec 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 Renitec 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 Renitec is augmented by antihypertensive agents that cause renin release (e.g. diuretics).

Other cardiovascular agents.

Renitec 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.)
Renitec 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 Renitec 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.

Antidiabetics.

Epidemiological studies have suggested that concomitant administration of ACE inhibitors and antidiabetic 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 antidiabetic 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.

Nonsteroidal anti-inflammatory drugs including selective cyclooxygenase-2 inhibitors.

Nonsteroidal 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 nonsteroidal anti-inflammatory drugs including selective cyclooxygenase-2 inhibitors, the coadministration 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 Renitec and other agents that affect the RAAS. Do not coadminister aliskiren with Renitec in patients with diabetes. Avoid use of aliskiren with Renitec 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).

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

There were no adverse effects on reproductive performance in male and female rats treated with 10 to 90 mg/kg/day of enalapril.
(Category D)
As with all ACE inhibitors, Renitec should not be taken during pregnancy. Pregnancy should be excluded before starting treatment with Renitec 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. Postmarketing 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 nondiabetic 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 foetotoxicty 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 Renitec is secreted in human milk. However, Renitec 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 breastfeeding should be discontinued.

4.8 Adverse Effects (Undesirable Effects)

Renitec has been evaluated for safety in more than 10,000 patients, including over 1000 patients treated for one year or more. Renitec 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 percent), dizziness (4.6 percent) and fatigue (2.8 percent). For the most part, adverse experiences were mild and transient in nature. Discontinuation of therapy was required in 6.0 percent 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 Renitec reporting adverse experiences was comparable to placebo.
Adverse experiences occurring in greater than one percent of patients treated with Renitec 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 percent 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 Renitec (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 Renitec 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 http://www.tga.gov.au/reporting-problems.

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 Renitec. The diuretic should, if possible, be discontinued for two to three days before beginning therapy with Renitec 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 Renitec 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 Renitec alone, a diuretic may be added.
Concomitant administration of Renitec 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 Renitec in the treatment of accelerated or malignant hypertension. Renitec, 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 Renitec 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 Renitec must be started under close medical supervision.
Blood pressure and renal function should be monitored closely both before and after starting treatment with Renitec (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 Renitec 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 Renitec does not imply that hypotension will recur during chronic therapy with Renitec 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 Renitec 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.)

4.7 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)).

4.9 Overdose

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. Enalaprilat may be removed from the general circulation by haemodialysis.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

7 Medicine Schedule (Poisons Standard)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

Sodium bicarbonate, lactose monohydrate, maize starch, pregelatinised maize starch, magnesium stearate, iron oxide red (10 mg and 20 mg Renitec tablets only), iron oxide yellow (20 mg Renitec tablets only).

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

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

6.4 Special Precautions for Storage

Store below 25°C.

6.5 Nature and Contents of Container

Supplied in blister packs of 30 tablets.

6.6 Special Precautions for Disposal

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

Summary Table of Changes