Consumer medicine information

APO-Valsartan

Valsartan

BRAND INFORMATION

Brand name

APO-Valsartan

Active ingredient

Valsartan

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

The name of your medicine is APO-Valsartan. It contains the active ingredient valsartan.

This medicine belongs to a group of medicines called angiotensin II receptor antagonists (AIIRAs).

It is used to treat:

Hypertension
This medicine is used to control high blood pressure, also called hypertension. Everyone has blood pressure. This pressure helps get your blood 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 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 it is to have your blood pressure checked regularly.

High blood pressure increases the workload of the heart and blood vessels. If it continues for a long time, it can damage the blood vessels in the brain, heart and kidneys. This can lead to stroke, heart failure or kidney failure. High blood pressure increases the risk of heart attacks. Lowering your blood pressure reduces the chance of these disorders happening.

Heart Failure
This medicine is used to treat 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. This medicine helps the heart to function better and relieves some of the symptoms of heart failure.

Heart Attack
This medicine is also used to treat people after they have had a heart attack (myocardial infarction), to reduce the risk of further heart damage and reduce further heart problems.

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

This medicine is not addictive.

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

Use in children

There is not enough information to recommend the use of valsartan in children (below 18 years of age).

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:

valsartan or 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
fainting or hayfever-like symptoms

Do not take valsartan if you are pregnant or intend to become pregnant. Valsartan may affect your developing baby if you take it during pregnancy.

Do not take valsartan if you are also taking other blood pressure lowering medicines containing aliskiren and have type 2 diabetes.

Do not take valsartan if you have liver disease caused by blockage in the bile duct or any other severe liver disease. Valsartan is not recommended if you have these conditions.

Do not take this medicine after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering. If it has expired or is damaged, return it to your pharmacist for disposal.

If you are not sure whether you should start taking valsartan, 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:

heart disease, heart failure or high blood pressure that is being treated with large doses of diuretics (also called water or fluid tablets), or are being treated with beta-blockers, aliskiren and/ or ACE-inhibitors
high blood pressure due to narrowing of the arteries in the kidney
any other kidney problems or are having dialysis
milder forms of liver disease
a hormonal disorder called primary hyperaldosteronism (Conn's syndrome), which can increase blood pressure
swelling, mainly of the face and throat, while taking other medicines (including an ACE inhibitor or aliskiren)
you have recently had severe vomiting or diarrhoea
you are severely limiting your salt intake.
obstructed blood flow through the heart from narrowing of valves (stenosis) or enlarged septum of the heart (HOCM)

Tell your doctor if you are breastfeeding or plan to breastfeed. It is not known if valsartan, the active ingredient, passes into the breast milk and could affect your baby.

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 and valsartan interfere with each other. These include:

ACE-inhibitors or aliskiren, which are also medicines used to treat hypertension or other heart conditions
beta-blockers, which are medicines used to treat hypertension or other heart conditions.
some diuretics (water or fluid pills) e.g. spironolactone, triamterene, amiloride
a class of anti-inflammatory medicines called NSAIDs and COX-2 inhibitors
potassium supplements, salt substitutes containing potassium, or other medications that may increase potassium levels (such as heparin)
some antibiotics (rifampicin), anti-rejection drugs (cyclosporin), antiretrovirals (ritonavir)
lithium used to treat conditions such as bipolar or schizophrenia.

If you are taking any of these, you may need a different dose, or you may need to take different medicines.

Your doctor may also check your kidney function.

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

How to take this medicine

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 label, ask your doctor or pharmacist for help.

How much to take

For hypertension, the usual dose is one 80 mg tablet once a day. If your blood pressure is still too high after 4 weeks, your doctor may increase the dose to 160 mg once a day, or from 160 mg to 320 mg once a day. If your blood pressure is still too high, your doctor may add a different type of blood pressure lowering medicine.

For heart failure, the usual starting dose is 40 mg twice daily. Your doctor may increase the dose gradually up to one 160 mg tablet twice daily.

Following a heart attack, treatment is generally started at a dose of 20 mg (half a 40 mg tablet) twice daily. Your doctor may increase the dose gradually up to 160 mg twice daily.

Do not stop taking your medicine or change your dosage without first checking with your doctor.

How to take it

Swallow the tablets with a full glass of water.

It does not matter if you take it after food or on an empty stomach, as long as you take it the same way each day.

If your stomach is upset after taking valsartan, always take it after a meal (e.g. breakfast).

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.

How long to take it for

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

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

It will take at least 4 weeks for this medicine to have its full effect. After that, it will be continued for as long as your doctor thinks is needed.

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 experiencing side effects.

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.

Too much of valsartan may make you feel dizzy, lightheaded or faint. You may experience rapid, shallow breathing or cold, clammy skin. Your heartbeat may be faster than usual.

This is because your blood pressure is too low.

While you are taking this medicine

Things you must do

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

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

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

If you become pregnant while taking valsartan, tell your doctor immediately. You should not take this medicine while you are pregnant.

Tell your doctor if, for any reason, you have not taken valsartan exactly as prescribed. Otherwise your doctor may think that it was not effective and change your treatment unnecessarily.

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

Keep all of your doctor's appointments so that your progress can be checked. Do this even if you feel well.

It is important to keep track of your progress. Your doctor will want to check your blood pressure and your kidney and liver function from time to time.

Things you must not do

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

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

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

Things to be careful of

Be careful when driving or operating machinery or doing jobs that require you to be alert while you are taking valsartan until you know how this medicine affects you. This medicine can cause tiredness, sleepiness or dizziness in some people. If you have these symptoms, do not drive or do anything else that could be dangerous.

If this medicine makes you feel dizzy or light-headed, be careful when getting up from a sitting or lying position. Dizziness can usually be prevented by getting up slowly and flexing leg muscles and toes to get the blood flowing. When getting out of bed, dangle your legs over the side for a minute or two before standing up.

Side effects

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

All medicines can have side effects. Sometimes they are serious but most of the time they are not.

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 or pharmacist if you notice any of the following and they worry you:

headache
dizziness, spinning sensation (vertigo)
sleepiness, tiredness or weakness
diarrhoea, constipation or wind
nausea (feeling sick), vomiting
loss of appetite, stomach pains or indigestion
dry cough, sore throat or hoarse voice
runny nose or congested sinuses
more infections than usual
pain in the back or joints
muscle pain or cramps
difficulty sleeping
feeling anxious
tingling or numbness in the hands or feet
problems with sexual function.

Tell your doctor immediately or go to the Accident and Emergency department at your nearest hospital if you notice any of the following:

signs of allergy such as cough, 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; fainting or hayfever-like symptoms
feeling of fast or irregular heart beat (pounding, racing, skipping beats)
chest pain
shortness of breath not caused by exercise, with swelling of legs or feet
tiredness or lack of energy, being short of breath when exercising, dizziness and looking pale
constant "flu-like" symptoms such as chills, fever, sore throat, aching joints, sores in mouth, swollen glands
severe dizziness or fainting
liver disease with nausea, vomiting, loss of appetite, feeling generally unwell, fever, itching, yellowing of the skin and eyes, and dark coloured urine

The above list includes serious side effects that may require medical attention.

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

Other side effects not listed above may also occur in some people.

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 this 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-Valsartan looks like

40 mg tablets: Yellow, modified, capsule shaped, film-coated tablets, engraved 'APO' on one side and 'VA' scored '40' on the other side. AUST R 185806. AUST R 185853.

80 mg tablets: Pale red, round, biconvex, film-coated tablets, engraved 'APO' on one side and 'VA' over '80' on the other side. AUST R 185814. AUST R 185854.

160 mg tablets: Yellow, modified, capsule shaped, film-coated tablets, engraved 'APO' on one side and 'VA160' on the other side. AUST R 185821. AUST R 185855.

320 mg tablets: Dark grey-violet, oval shaped, film-coated tablets, engraved 'APO' on one side and 'VA320' on the other side. AUST R 185826. AUST R 185856.

Blister packs of 7, 14, 28, 30, 56 tablets

Bottle packs of 28, 100, 500 tablets

Ingredients

Each tablet contains 40, 80, 160 or 320 mg of valsartan as the active ingredient.

It also contains the following inactive ingredients:

powdered cellulose
calcium hydrogen phosphate dihydrate
croscarmellose sodium
colloidal anhydrous silica
magnesium stearate
hypromellose
hyprolose
macrogol 8000
titanium dioxide
iron oxide yellow iron oxide red purified water
The 160 and 320 mg tablets also contain: iron oxide black.

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

Sponsor

Apotex Pty Ltd
16 Giffnock Avenue
Macquarie Park, NSW 2113

APO and APOTEX is a registered trade mark of Apotex Inc.

This leaflet was last updated in: July 2019.

Published by MIMS September 2019

BRAND INFORMATION

Brand name

APO-Valsartan

Active ingredient

Valsartan

Schedule

1 Name of Medicine

Valsartan.

6.7 Physicochemical Properties

Valsartan is a white to practically white fine powder. It is soluble in ethanol and methanol and slightly soluble in water.
Chemical Name: N-pentanoyl-N- [2'-(1H-tetrazol-5-yl) biphenyl-4ylmethyl]-L-valine. Molecular Formula: C₂₄H₂₉N₅O₃. Molecular Weight: 435.5.

Chemical structure.

CAS number.

137862-53-4.

2 Qualitative and Quantitative Composition

Each tablet contains 40, 80, 160 or 320 mg of valsartan as the active ingredient.
For the full list of excipients see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Valsartan 40 mg tablets.

Yellow, modified, capsule shaped, film-coated tablets, engraved 'APO' on one side and 'VA' scored '40' on the other side.

Valsartan 80 mg tablets.

Pale red, round, biconvex, film-coated tablets, engraved 'APO' on one side and 'VA' over '80' on the other side.

Valsartan 160 mg tablets.

Yellow, modified, capsule shaped, film-coated tablets, engraved 'APO' on one side and 'VA160' on the other side.

Valsartan 320 mg tablets.

Dark grey-violet, oval shaped, film-coated tablets, engraved 'APO' on one side and 'VA320' on the other side.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

The active hormone of the renin-angiotensin-aldosterone system (RAAS) is angiotensin II, which is formed from angiotensin I through the action of angiotensin converting enzyme (ACE). Angiotensin II binds to specific receptors located in the cell membranes of various tissues. It has a wide variety of physiological effects, including both direct and indirect involvement in the regulation of blood pressure. As a potent vasoconstrictor, angiotensin II exerts a direct pressor response. In addition, it promotes sodium retention and stimulation of aldosterone secretion.
Valsartan is an orally active, potent and specific angiotensin II (Ang II) receptor antagonist. It acts selectively on the AT₁ receptor subtype, which is responsible for the known actions of angiotensin II. The AT₂ receptor subtype has not been definitely shown to be associated with cardiovascular homeostasis. Valsartan does not exhibit any partial agonist activity at the AT₁ receptor and has about a 20,000-fold greater affinity for the AT₁ receptor than for the AT₂ receptor.
Valsartan does not inhibit ACE, also known as kininase II, which converts Ang I to Ang II and degrades bradykinin. Since there is no effect on ACE and no potentiation of bradykinin or substance P, angiotensin II antagonists are unlikely to be associated with cough. In clinical trials where valsartan was compared with an ACE inhibitor, the incidence of dry cough was significantly (P < 0.05) less in patients treated with valsartan than in those treated with an ACE inhibitor (2.4% versus 7.9%, respectively). In a clinical trial of patients with a history of dry cough during ACE inhibitor therapy, 19.5% of trial subjects receiving valsartan and 19.0% of those receiving a thiazide diuretic experienced cough compared with 68.9% of those treated with an ACE inhibitor (P < 0.05).
Valsartan does not bind to or block other hormone receptors or ion channels known to be important in cardiovascular regulation.
Administration of valsartan to patients with hypertension results in reduction of blood pressure without affecting pulse rate. In most patients after administration of a single oral dose, onset of antihypertensive activity occurs within 2 hours and the peak reduction in blood pressure is achieved within 4-6 hours. The antihypertensive effect persists over 24 hours after dose administration. During repeated administration, the maximum reduction in blood pressure with any dose is generally attained within 2-4 weeks and is sustained during long-term therapy. When valsartan is combined with hydrochlorothiazide, a significant additional reduction in blood pressure is achieved.
Abrupt withdrawal of valsartan has not been associated with rebound hypertension or other adverse clinical events.
In multiple dose studies in hypertensive patients valsartan had no notable effects on total cholesterol, fasting triglycerides, or fasting serum glucose. Valsartan has no uricosuric effect.

Heart failure.

Haemodynamics and plasma neurohormones were measured in NYHA class II-IV heart failure patients with pulmonary capillary wedge pressure > 15 mmHg in 2 short-term, chronic therapy studies. In one study, which included patients chronically treated with ACE inhibitors, single and multiple doses of valsartan given in combination with an ACE inhibitor improved haemodynamics including pulmonary capillary wedge pressure (PCWP), pulmonary artery diastolic pressure (PAD) and systolic blood pressure (SBP). Reductions were observed in plasma aldosterone (PA) and plasma norepinephrine (PNE) levels after 28 days of treatment. In the second study, which included only patients untreated with ACE inhibitors for at least 6 months prior to enrollment, valsartan significantly improved PCWP, systemic vascular resistance (SVR), cardiac output (CO) and SBP after 28 days of treatment. In the long-term Valsartan Heart Failure Trial, plasma norepinephrine and brain natriuretic peptide (BNP) were significantly reduced from baseline in the valsartan group compared to placebo.

Clinical trials.

Hypertension.

Treatment with valsartan 320 mg.

A randomised, double-blind, multi-centre, active-controlled, parallel-group study in patients with hypertension was designed to evaluate the efficacy and safety of once daily dose of valsartan 320 mg (n = 1873) compared to valsartan 160 mg (n = 1884) after a 4 week run-in period with valsartan 160 mg o.d. Blood pressure lowering effects of 4 weeks treatment were measured in patients aged 18-80 years with uncomplicated mild to moderate hypertension (mean sitting diastolic blood pressure [MSDBP] ≥ 95 mmHg and ≤ 109 mmHg). Patients with severe or malignant hypertension, those who were unable to cease all antihypertensive agents for 2 weeks and those who had a clinically significant disorder that might affect study outcome or patients safety were excluded from participation in this study.
The primary efficacy measure was change in trough MSDBP from baseline to endpoint, and the secondary efficacy measure was changes in trough MSDBP from baseline to endpoint in patients not adequately controlled with valsartan 160 mg.
Results for both MSDBP and mean sitting diastolic blood pressure (MSSBP) are reported in Tables 4 and 5.

Heart failure.

The Valsartan Heart Failure Trial was a randomised, controlled multinational clinical trial of valsartan compared with placebo on morbidity and mortality in NYHA class II (62%), III (36%) and IV (2%) heart failure patients receiving usual therapy with LVEF < 40% and left ventricular internal diastolic diameter (LVIDD) > 2.9 cm/m². The study enrolled 5010 patients in 16 countries who were randomised to receive either valsartan or placebo in addition to all other appropriate therapy including ACE inhibitors (93%), diuretics (86%), digoxin (67%) and beta-blockers (36%). The mean duration of follow-up was nearly two years. The mean daily dose in the study was 254 mg. The study had two primary endpoints: all-cause mortality (time to death) and heart failure morbidity (time to first morbid event) defined as death, sudden death with resuscitation, hospitalisation for heart failure or administration of intravenous inotropic or vasodilator drugs for four hours or more without hospitalisation.
In the trial population no statistically significant improvement in mortality was observed among valsartan treated patients compared to those who received placebo. Morbidity was significantly reduced by 13.2% with valsartan compared to placebo treatment. The primary benefit was a 27.5% reduction in the risk for time to first heart failure hospitalisation. There was no evidence of additional benefit from concurrent use of valsartan with ACE inhibitors. An increased rate of mortality was observed in patients taking the triple combination of a beta-blocker, an ACE inhibitor and valsartan.
Valsartan-treated patients showed significant improvement in NYHA class, and heart failure signs and symptoms, including dyspnea, fatigue, oedema and rales compared to placebo. Patients on valsartan had a better quality of life as demonstrated by change in the Minnesota Living with Heart Failure Quality of Life score from baseline at endpoint than placebo. Ejection fraction in valsartan-treated patients was significantly increased and LVIDD significantly reduced from baseline at endpoint compared to placebo.

Post-myocardial infarction.

The Valsartan In Acute myocardial iNfarcTion trial (VALIANT) was a randomised, controlled, multinational, double blind study in 14,703 patients with acute myocardial infarction and signs, symptoms or radiological evidence of congestive heart failure and/or evidence of left ventricular systolic dysfunction (manifested as an ejection fraction ≤ 40% by radionuclide ventriculography or ≤ 35% by echocardiography or ventricular contrast angiography). Patients with systolic blood pressure below 100 mmHg, serum creatinine above 221 micromol/L (2.5 mg/dL), and significant right ventricular myocardial infarction were excluded.
Patients were randomised within 12 hours to 10 days after the onset of myocardial infarction symptoms to one of three treatment groups: valsartan given 4-8 days (median 6 days) after myocardial infarction, captopril given 4-8 days (median 6 days) after myocardial infarction, or the combination of both. Physicians were advised to titrate patients up to at least 80 mg valsartan twice daily at 15 days after randomisation or at hospital discharge, and that the target maximum dose of 160 mg valsartan twice daily should be reached after 3 months. The mean treatment duration was two years. The mean daily dose of valsartan in the monotherapy group was 217 mg. Baseline therapy included acetylsalicylic acid (91%), beta-blockers (70%), ACE inhibitors (40%), thrombolytics (35%), and statins (34%). The population studied was 69% male, 94% Caucasian, and 53% were 65 years of age or older. The primary endpoint was time to all-cause mortality.
Valsartan was as effective as captopril in reducing all-cause mortality after myocardial infarction, as summarised in Table 6. Valsartan was also effective in prolonging the time to and reducing cardiovascular mortality, hospitalisation for heart failure, recurrent myocardial infarction, resuscitated cardiac arrest, and nonfatal stroke (secondary composite endpoint).

Since this was a trial with an active control (captopril), an additional analysis of all-cause mortality was performed to estimate how valsartan would have performed versus placebo. Using the results of the previous reference myocardial infarction trials - SAVE, AIRE, and TRACE - the estimated effect of valsartan preserved 99.6% of the effect of captopril (97.5% CI = 60-139%). Combining valsartan with captopril did not add further benefit over captopril alone, therefore this combination is not recommended. There was no difference in all-cause mortality based on age, gender, race, baseline therapies or underlying disease.

5.2 Pharmacokinetic Properties

Absorption.

Peak plasma concentrations are reached 2 to 4 hours after dosing. The amount absorbed varies widely. Mean absolute bioavailability is 23% and the bioavailability relative to an oral solution is 59%.
The pharmacokinetics of valsartan are linear over the dose range 80-320 mg. There is no change in the kinetics of valsartan on repeated administration and little accumulation when dosed once daily. Plasma concentrations are similar in males and females.
When valsartan is given with food, the area under the plasma concentration time curve (AUC) of valsartan is reduced by 48% although, from about 8 h post dosing, plasma valsartan concentrations are similar for the fed and fasted group.

Distribution.

Valsartan is highly bound to serum protein (94-97%), mainly serum albumin. Steady-state volume of distribution is low (about 17 L) indicating that valsartan does not distribute into tissues extensively.

Metabolism.

Valsartan does not undergo extensive biotransformation. Only approximately 25% of absorbed drug is metabolised. The primary metabolite is valeryl 4-hydroxy valsartan, which is pharmacologically inactive. The enzyme(s) responsible for valsartan metabolism have not been identified.

Excretion.

Valsartan shows bi-exponential decay kinetics with a t_1/2α of about 1 h and a t_1/2β of about 9.5 hours. After oral dosing, 83% of the dose is excreted in the faeces and 13% in the urine, mainly as unchanged compound. Following intravenous administration, renal clearance of valsartan accounts for about 30% of total plasma clearance. Plasma clearance is relatively slow (about 2 L/h) when compared with hepatic blood flow (about 30 L/h).

Effect of age and disease on pharmacokinetics.

Elderly patients.

Exposure (measured by AUC) to valsartan is higher by 70% and the half-life is longer by 35% in the elderly than in the young. No dosage adjustment is necessary (see Section 4.2 Dose and Method of Administration).

Children.

The pharmacokinetics of valsartan have not been investigated in patients less than 18 years of age.

Heart failure.

The average time to peak concentration and elimination half-life of valsartan in heart failure patients are similar to that observed in healthy volunteers. AUC and C_max values of valsartan increase linearly and are almost proportional with increasing dose over the clinical dosing range (40 to 160 mg twice a day). The average accumulation factor is about 1.7. The apparent clearance of valsartan following oral administration is approximately 4.5 L/h. Age does not affect the apparent clearance in heart failure patients.

Impaired renal function.

As expected for a compound where renal clearance accounts for only 30% of total plasma clearance, there is no apparent correlation between renal function (measured by creatinine clearance) and systemic exposure to valsartan (measured by AUC) in patients with different degrees of renal failure. A trial in 5 normotensive patients undergoing haemodialysis demonstrated that complete loss of renal function does not lead to a gross increase in the exposure to valsartan and does not have a major impact on the kinetics of valsartan. This study also confirmed that valsartan is not removed from the plasma by haemodialysis.

Impaired hepatic function.

About 70% of the absorbed dose is excreted in the bile, mainly as unchanged compound. The AUC with valsartan has been observed to approximately double in patients with mild or moderate hepatic impairment including patients with biliary obstructive disorders (see Section 4.4 Special Warnings and Precautions for Use, Use in hepatic impairment).

5.3 Preclinical Safety Data

Genotoxicity.

Genetic toxicology studies showed that valsartan does not cause gene mutation in bacterial or mammalian cells, nor does it induce chromosomal damage in vitro or in vivo.

Carcinogenicity.

In animal studies, there was no clear evidence of carcinogenic activity when valsartan was administered in the diet to male and female mice at doses up to 160 mg/kg/day for two years, but systemic exposure (plasma AUC value) at this dose level was lower than that achieved in humans. There was no clear evidence of carcinogenic activity in male or female rats at concentrations approximately 1.5 times the concentrations achieved in humans at the maximum recommended dose (160 mg bid).

4 Clinical Particulars

4.1 Therapeutic Indications

Treatment of hypertension.
Treatment of heart failure (NYHA class II-IV) in patients receiving usual therapy (e.g. diuretics, digitalis) who are intolerant to ACE inhibitors.
To improve survival following myocardial infarction in clinically stable patients with clinical or radiological evidence of left ventricular failure and/or with left ventricular systolic dysfunction (see Section 5.1 Pharmacodynamic Properties, Clinical trials).

4.3 Contraindications

Hypersensitivity to any of the components of valsartan.
Pregnancy (see Section 4.6 Fertility, Pregnancy and Lactation, Use in pregnancy).
Severe hepatic impairment; biliary cirrhosis and cholestasis.
Concomitant use with aliskiren in patients with Type 2 diabetes mellitus (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

4.4 Special Warnings and Precautions for Use

Use in special patient groups. Sodium- and/or volume-depleted patients.

In severely sodium-depleted and/or volume-depleted patients, such as those receiving high doses of diuretics, symptomatic hypotension may occur in rare cases after initiation of therapy with valsartan. Sodium and/or volume depletion should be corrected before starting treatment with valsartan, for example, by reducing the diuretic dose or treatment should be commenced under close medical supervision.
If hypotension occurs, the patient should be placed in the supine position and, if necessary, given an intravenous infusion of normal saline. Treatment with valsartan can be continued once the blood pressure has stabilised.

Renal artery stenosis.

There has been no long-term use of valsartan in patients with unilateral or bilateral renal artery stenosis. Short-term administration of valsartan to twelve patients with renovascular hypertension secondary to unilateral renal artery stenosis did not induce any significant changes in renal haemodynamics, serum creatinine, or blood urea nitrogen (BUN). However, since other drugs that affect the renin-angiotensin-aldosterone system (RAAS) may increase blood urea and serum creatinine in patients with bilateral or unilateral renal artery stenosis, monitoring of both parameters is recommended as a safety measure.

Use in renal impairment.

In patients with severe renal impairment (creatinine clearance < 30 mL/min) the dose of valsartan should not exceed 80 mg per day.
The use of angiotensin receptor antagonists (ARBs) including valsartan or angiotensin converting enzyme inhibitors (ACEIs) with aliskiren should be avoided in patients with severe renal impairment (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
As a consequence of inhibiting the renin-angiotensin-aldosterone system, increases of blood urea and serum creatinine and changes in renal function including renal failure (very rarely) have been reported, particularly in patients with pre-existing renal dysfunction or those with severe cardiac insufficiency. In patients whose renal function may depend on the activity of the renin-angiotensin-aldosterone system (e.g. patients with severe congestive heart failure) treatment with angiotensin converting enzyme inhibitors and angiotensin receptor antagonists has been associated with oliguria and/or progressive azotemia and (rarely) acute renal failure and/or death. It cannot be excluded that valsartan could behave similarly.

Use in hepatic impairment.

In patients with mild to moderate hepatic impairment without cholestasis, valsartan should be used with caution (see Section 5.2 Pharmacokinetic Properties, Impaired hepatic function). The daily dose of valsartan should not exceed 80 mg. Patients with severe hepatic impairment, biliary cirrhosis or cholestasis should not take valsartan (see Section 4.3 Contraindications).

Hepatic injury.

Cases of clinically significant liver disease have occurred with some angiotensin II receptor antagonists. Hepatitis has been reported rarely with valsartan.

Heart failure/ post myocardial infarction.

Use of valsartan in patients with heart failure or post-myocardial infarction commonly results in some reduction in blood pressure, but discontinuation of therapy because of continuing symptomatic hypotension is not usually necessary provided dosing instructions are followed. Patients with more complicated post-myocardial infarction courses may be at increased risk for hypotension and/or renal dysfunction. Caution should be observed when initiating therapy in patients with heart failure or post-myocardial infarction. An assessment of renal function should always be conducted in patients with heart failure or post-myocardial infarction.

Concomitant therapy in patients with heart failure.

An increase in the mortality rate among patients who received a combination of valsartan, ACE inhibitors and beta-blockers has been observed in clinical trials. Concurrent administration of ACE inhibitors, beta-blockers and valsartan is not recommended (see Section 5.1 Pharmacodynamic Properties, Clinical trials).

Angioedema.

Angioedema, including swelling of the larynx and glottis, causing airway obstruction and/or swelling of the face, lips, pharynx and/or tongue has been reported in patients treated with valsartan; some of these patients previously experienced angioedema with other drugs including ACE inhibitors. Valsartan should be immediately discontinued in patients who develop angioedema, and should not be re-administered.

Dual blockade of the renin-angiotensin system (RAS).

Caution is required while co-administering ARBs, including valsartan, with other agents blocking the RAS such as ACEIs or aliskiren (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Patients receiving potassium sparing diuretics or potassium containing products.

If concomitant medication is considered necessary, monitoring of serum potassium is advised (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Primary hyperaldosteronism.

Patients with primary hyperaldosteronism will not generally respond to antihypertensive drugs acting through the renin-angiotensin-aldosterone system therefore use of valsartan in these patients is not recommended.

Aortic and mitral valve stenosis, hypertrophic obstructive cardiomyopathy.

As with all other vasodilators, special caution is indicated in patients suffering from haemodynamically relevant aortic or mitral stenosis, or hypertrophic obstructive cardiomyopathy (HOCM).

Use in the elderly.

In the controlled clinical trials of valsartan, 1214 (36.2%) of hypertensive patients treated with valsartan were > 65 years and 265 (7.9%) were > 75 years. No overall difference in the efficacy or safety of valsartan was observed in this patient population.
Of the 2511 patients with heart failure randomised to valsartan in the Valsartan Heart Failure Trial, 45% (1141) were 65 years or older. No special precautions are required when using valsartan in elderly patients with heart failure.

Paediatric use.

The safety and efficacy of valsartan in children and adolescents (below the age of 18 years) have not been established.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Combination use of ACE inhibitors or angiotensin receptor antagonist, anti-inflammatory drugs (NSAIDs or COX-2 inhibitors) and thiazide diuretics.

When angiotensin II antagonists are administered simultaneously with NSAIDs, attenuation of the antihypertensive effect may occur.
The use of an ACE inhibiting drug (ACE-inhibitors) 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. Concomitant use of angiotensin II antagonists and NSAIDs in patients who are elderly, volume-depleted (including those on diuretic therapy) or have compromised renal function may lead to an increased risk of worsening renal function, including possible acute renal failure. 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 when initiating or modifying treatment.

Dual blockade of the renin-angiotensin system (RAS) with ARBs, ACEIs or aliskiren.

The concomitant use of ARBs, including valsartan, with other agents acting on the RAS is associated with an increased incidence of hypotension, hyperkalaemia, and changes in renal function compared to monotherapy. It is recommended to monitor blood pressure, renal function and electrolytes in patients on valsartan and other agents that affect the RAS (see Section 4.4 Special Warnings and Precautions for Use).
The concomitant use of ARBs including valsartan, or ACEIs, with aliskiren should be avoided in patients with severe renal impairment (GFR < 30 mL/min) (see Section 4.4 Special Warnings and Precautions for Use).
The concomitant use of ARBs including valsartan, or ACEIs, with aliskiren is contraindicated in patients with Type 2 diabetes mellitus (see Section 4.3 Contraindications).

Potassium.

Concomitant use of potassium-sparing diuretics (e.g. spironolactone, triamterene, amiloride), potassium supplements or salt substitutes containing potassium or other drugs that may increase potassium levels (heparin, etc) may lead to increases in serum potassium and in heart failure patients, may lead to increases in serum creatinine. If co-medication is considered necessary monitoring of serum potassium is advisable (see Section 4.4 Special Warnings and Precautions for Use, Use in special patient groups).

Lithium salts.

Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with ACE inhibitors or angiotensin II receptor antagonists, including valsartan. Therefore, careful monitoring of serum lithium levels is recommended during concomitant use. If a diuretic is also used, the risk of lithium toxicity may presumably be increased further with valsartan.

Hepatic transporters.

Co-administration with inhibitors of the hepatic uptake transporter OATP1B1 (such as rifampicin, cyclosporin) or hepatic efflux transporter MRP2 (e.g. ritonavir) may increase the systemic exposure to valsartan.
No drug interactions of clinical significance have yet been found. Compounds which have been studied in clinical trials include cimetidine, warfarin, frusemide, digoxin, atenolol, indomethacin, hydrochlorothiazide, amlodipine and glibenclamide.
As valsartan is not metabolised to a significant extent, clinically relevant drug-drug interactions in the form of metabolic induction or inhibition of the cytochrome P450 system are not expected with valsartan. Although valsartan is highly bound to plasma proteins, in vitro studies have not shown any interaction at this level with a range of molecules which are also highly protein-bound, such as diclofenac, frusemide, and warfarin.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Fertility of male and female rats was not affected at oral doses up to 200 mg/kg/day, with systemic exposure similar to that in human patients at the maximum recommended dose.
(Category D)
Drugs that act on the renin-angiotensin-aldosterone system (RAAS) can cause fetal and neonatal morbidity and death when administered to pregnant women. Several dozen cases have been reported in the world literature in patients who were taking angiotensin converting enzyme inhibitors (a specific class of drugs acting on the RAAS).
There have been reports of spontaneous abortion, oligohydramnios and newborn renal dysfunction, when pregnant women have inadvertently taken valsartan. As for any drug that also acts directly on the RAAS, valsartan should not be used during pregnancy (see Section 4.3 Contraindications) or in women planning to become pregnant. Physicians prescribing any agents acting on the RAAS should counsel women of childbearing potential about the potential risk of these agents during pregnancy. When pregnancy is detected, valsartan should be discontinued as soon as possible.
The use of drugs that act directly on the renin-angiotensin-aldosterone system (RAAS) during the second and third trimesters of pregnancy has been associated with fetal and neonatal injury, including hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure and death. Oligohydramnios has also been reported, presumably resulting from decreased fetal renal function.
Oligohydramnios in this setting has been associated with fetal limb contractures, craniofacial deformation and hypoplastic lung development. Prematurity, intrauterine growth retardation and patent ductus arteriosus have also been reported, although it is not clear whether these occurrences were due to exposure to the drug. In addition, in retrospective data, first trimester use of ACE inhibitors has been associated with a potential risk of birth defects.
Infants with histories of in utero exposure to an angiotensin II receptor antagonist should be closely observed for hypotension, oliguria and hyperkalaemia.
No teratogenic effects were observed when valsartan was administered orally to mice and rats at a dose of 600 mg/kg/day and to rabbits at a dose of 10 mg/kg/day during the period of organogenesis. However, fetal losses were observed at the highest dose level in rabbits, and fetal weight was reduced at 600 mg/kg/day in rats and at 5 mg/kg/day in rabbits.
Administration of 600 mg/kg/day valsartan to rats prior to parturition and during lactation caused a decrease in birth weight, a reduction in postnatal growth and survival, and a slight delay in physical development of the offspring. A reduction of red blood cell parameters and evidence of changes in renal haemodynamics were observed at 200-600 mg/kg/day.
Although valsartan is excreted in the milk of lactating rats, it is not known whether it is excreted in human milk. A peri/postnatal study in rats showed reductions in postnatal growth and survival, and a slight delay in physical development of the offspring when valsartan was administered to rats prior to parturition and during lactation at oral dose levels greater than 200 mg/kg/day. Thus, it is not advisable to use valsartan in lactating mothers.

4.8 Adverse Effects (Undesirable Effects)

The following summary of adverse reactions is based on clinical trials in hypertension, heart failure and post-myocardial infarction treated with various doses of valsartan (10 mg-320 mg daily). It also includes post marketing reports. The incidence of reported AEs in clinical trials did not appear to be related to dose or duration of treatment. Therefore, AEs occurring on all doses of valsartan were pooled. As well, the incidence of AEs was not associated with gender, age or race.
Frequencies are defined as: very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1000, < 1/100); rare (≥ 1/10,000, < 1/1000); very rare (< 1/10,000). See Table 1.

Hypertension.

In placebo-controlled trials in which 2542 patients with hypertension were treated with various doses of valsartan (10 mg-320 mg), the study drug showed an overall incidence of adverse events (AEs) comparable with that of placebo.
A 6-month open-label extension trial involving 642 patients with hypertension treated with valsartan 320 mg showed an overall incidence of AEs comparable with that observed in placebo-controlled trials.
All adverse events with an incidence of 1% or more in the valsartan treatment group are included in Table 2, irrespective of their causal association with the study drug.

Other adverse experiences that occurred in controlled clinical trials of patients treated with valsartan (> 0.2% of valsartan patients) are listed below. It cannot be determined whether these events were causally related to valsartan. See Table 3.

Other reported events seen less frequently in clinical trials included chest pain, syncope, anorexia and vomiting.

Heart failure.

The adverse experience profile of valsartan in heart failure patients was consistent with the pharmacology of the drug and the health status of the patients. In the Valsartan Heart Failure Trial (Val-HeFT), comparing valsartan in total daily doses up to 320 mg (n = 2506) to placebo (n = 2494), 9.9% of valsartan patients discontinued for adverse events vs. 7.3% of placebo patients.
Table 1 includes adverse reactions from double blind short term heart failure trials, including the first 4 months of the ValHeFT, and drug-related adverse events with an incidence greater than 1% and more frequent in valsartan treated patients than in placebo treated patients. All patients received standard drug therapy for heart failure, frequently as multiple medications which could include diuretics, digitalis, beta-blockers, or ACE inhibitors.

Post-myocardial infarction.

In the double-blind, randomised, active-controlled, parallel-group VALIANT trial comparing the efficacy and safety of long-term treatment with valsartan, captopril and their combination in high risk patients after myocardial infarction, the safety profile of valsartan was consistent with the pharmacology of the drug and the background diseases, cardiovascular risk factors, and clinical course of patients treated in the post-myocardial infarction setting.
Serious adverse events (SAEs) were primarily cardiovascular and generally related to the underlying disease as reflected in the primary efficacy endpoint of all-cause mortality. Nonfatal SAEs with suspected study drug relationship observed with an incidence of ≥ 0.1% are included in Table 1.
The percentage of permanent discontinuations due to adverse events was 5.8% in valsartan treated patients and 7.7% in captopril-treated patients. Permanent discontinuation for hypotension or renal adverse events occurred in 1.4% and 1.1%, respectively, of valsartan treated patients, and in 0.8% and 0.8%, respectively, of captopril-treated patients.

Post-marketing experience.

Elevated liver enzymes and very rare reports of hepatitis. Angioedema and rash have been reported rarely. Pruritus and other hypersensitivity/allergic reactions including serum sickness and vasculitis have been reported very rarely. There have been very rare cases of bleeding and thrombocytopenia. Very rare cases of impaired renal function have also been reported. Rare cases of rhabdomyolysis have been reported in patients receiving angiotensin II receptor blockers. Dermatitis bullous and hyponatraemia of unknown incidence have been reported.

Laboratory findings.

In controlled clinical trials, clinically important changes in standard laboratory parameters were rarely associated with administration of valsartan.

Creatinine.

Minor elevations in creatinine occurred in 0.8% of patients taking valsartan and 0.6% given placebo in controlled trials of hypertensive patients. In heart failure patients, increases in serum creatinine greater than 50% were observed in 3.9% of valsartan treated patients compared to 0.9% of placebo treated patients. In post-myocardial infarction patients, doubling of serum creatinine was observed in 4.2% of valsartan-treated patients, 4.8% of valsartan plus captopril-treated patients, and 3.4% of captopril-treated patients.

Blood urea nitrogen.

In heart failure trials, increases in blood urea nitrogen (BUN) greater than 50% were observed in 16.6% of patients treated with valsartan compared to 6.3% of patients treated with placebo.

Haematocrit and haemoglobin.

Greater than 20% decreases in haemoglobin and haematocrit were observed in 0.4% and 0.8% respectively, of valsartan patients compared with 0.1% and 0.1% in placebo-treated patients. One valsartan patient discontinued treatment for microcytic anaemia.

Liver function tests.

Occasional elevations (greater than 150%) of liver function values were reported in patients treated with valsartan. Three patients (< 0.1%) treated with valsartan discontinued treatment for elevated liver function values. Elevated liver enzymes have also been reported in post-marketing surveillance.

Neutropenia.

Neutropenia was observed in 1.9% of patients treated with valsartan and 0.8% of patients treated with placebo.

Serum potassium.

In patients with hypertension, increases in serum potassium greater than 20% were observed in 4.4% of patients treated with valsartan compared to 2.9% of placebo treated patients. No patients treated with valsartan discontinued therapy for hyperkalaemia. In heart failure patients, increases in serum potassium greater than 20% were observed in 10.0% of valsartan treated patients compared to 5.1% of placebo treated patients.

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 and contact Apotex Medical Information Enquiries/Adverse Drug Reaction Reporting on 1800 195 055.

4.2 Dose and Method of Administration

Dosage.

Dosage in adults only.

Hypertension.

The recommended dose of valsartan is 80 mg once daily, irrespective of race, age or gender. The maximum antihypertensive effect is seen after 4 weeks. In patients whose blood pressure is not adequately controlled, the daily dose may be increased to 160 mg. If additional blood pressure reduction is required, a diuretic may be added or the dose can be increased further to a maximum of 320 mg. Valsartan may also be administered with other antihypertensive agents.

Heart failure.

The recommended starting dose of valsartan is 40 mg twice daily. Titration upwards to 80 mg and 160 mg twice daily should be done to the highest dose tolerated by the patient. Consideration should be given to reducing the dose of concomitant diuretics. The maximum daily dose administered in clinical trials is 320 mg in divided doses.
An assessment of renal function should always be conducted in patients with heart failure.
Valsartan has not been demonstrated to reduce mortality in patients with cardiac failure. No additional benefit on morbidity has been demonstrated from the concurrent use of valsartan and ACE inhibitors. Concurrent use of valsartan and an ACE inhibitor is not recommended.

Post-myocardial infarction.

Therapy may be initiated as early as 12 hours after a myocardial infarction. After an initial dose of 20 mg twice daily, valsartan therapy should be titrated to 40 mg, 80 mg, and 160 mg twice daily over the next few weeks. The starting dose is provided by the 40 mg divisible tablet.
Achievement of the target dose of 160 mg twice daily should be based on the patient's tolerability to valsartan during titration. If symptomatic hypotension or renal dysfunction occurs, consideration should be given to a dosage reduction. Evaluation of post-myocardial infarction patients should always include assessment of renal function.
Valsartan may be used in patients treated with other post-myocardial infarction therapies, e.g. thrombolytics, acetylsalicylic acid, beta-blockers, and statins.
Valsartan should be administered consistently with or without food (see Section 5.2 Pharmacokinetic Properties).
No initial dosage adjustment is required in the elderly.

Renal impairment.

For patients with severe renal impairment, a maximum daily dose of 80 mg per day is recommended (see Section 4.4 Special Warnings and Precautions for Use; Section 5.2 Pharmacokinetic Properties).

Hepatic impairment.

Use in patients with mild to moderate hepatic impairment.

A daily dose of 80 mg should not be exceeded (see Section 4.4 Special Warnings and Precautions for Use; Section 5.2 Pharmacokinetic Properties). Patients with severe hepatic impairment, biliary cirrhosis or cholestasis should not take valsartan (see Section 4.3 Contraindications).

Dosage in children and adolescents (below the age of 18 years).

The safety and efficacy of valsartan in children and adolescents (below the age of 18 years) have not been established.

4.7 Effects on Ability to Drive and Use Machines

As with other antihypertensive agents, it is advisable to exercise caution when driving or operating machinery.

4.9 Overdose

Overdose with valsartan may result in marked hypotension, which could lead to depressed level of consciousness, circulatory collapse and/or shock. The patient should always be given a sufficient amount of activated charcoal. Otherwise, the usual treatment would be intravenous infusion of normal saline solution. Valsartan is not removed 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

Powdered cellulose, calcium hydrogen phosphate dihydrate, croscarmellose sodium, colloidal anhydrous silica, magnesium stearate, hypromellose, hyprolose, macrogol 8000, titanium dioxide, iron oxide yellow, iron oxide red, purified water.
The 160 and 320 mg tablets also contain iron oxide black.

6.2 Incompatibilities

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

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 heat and moisture.

6.5 Nature and Contents of Container

APO-Valsartan 40 mg tablets.

Blister Pack (Clear PVC/PE/PVDC/Aluminium silver foil) of 7, 14, 28, 30 and 56 tablets. AUST R number 185806.
Bottles (white, round HDPE bottle with blue child-resistant cap) of 28 tablets and (white, round HDPE bottle with blue PP Lift N Peel cap) 100 and 500 tablets. AUST R number 185853.

APO-Valsartan 80 mg tablets.

Blister Pack (Clear PVC/PE/PVDC/Aluminium silver foil) of 7, 14, 28, 30 and 56 tablets. AUST R number 185814.
Bottles (white, round HDPE bottle with blue child-resistant cap) of 28 tablets and (white, round HDPE bottle with blue PP Lift N Peel cap) 100 and 500 tablets. AUST R number 185854.

APO-Valsartan 160 mg tablets.

Blister Pack (Clear PVC/PE/PVDC/Aluminium silver foil) of 7, 14, 28, 30 and 56 tablets. AUST R number 185821.
Bottles (white, round HDPE bottle with blue child-resistant cap) of 28 tablets and (white, round HDPE bottle with blue PP Lift N Peel cap) 100 and 500 tablets. AUST R number 185855.

APO-Valsartan 320 mg tablets.

Blister Pack (Clear PVC/PE/PVDC/Aluminium silver foil) of 7, 14, 28, 30 and 56 tablets. AUST R number 185826.
Bottles (white, round HDPE bottle with blue child-resistant cap) of 28 tablets and (white, round HDPE bottle with blue PP Lift N Peel cap) 100 and 500 tablets. AUST R number 185856.
Not all strengths, pack types and/or pack sizes may be available.
APO and APOTEX are registered trademarks of Apotex Inc.

6.6 Special Precautions for Disposal

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

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