Consumer medicine information

NNA-Ezetimibe/Simvastatin

Ezetimibe + Simvastatin

BRAND INFORMATION

Brand name

NNA-Ezetimibe/Simvastatin

Active ingredient

Ezetimibe + Simvastatin

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using NNA-Ezetimibe/Simvastatin.

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

NNA-Ezetimibe/Simvastatin helps to lower cholesterol and triglyceride levels. It is used in people whose cholesterol levels are too high and when diet alone cannot lower these levels adequately.

Cholesterol

Cholesterol is one of several fatty substances found in the bloodstream. Your total cholesterol is made up mainly of LDL and HDL cholesterol.

LDL cholesterol is often called 'bad' cholesterol because it can build up in the walls of your arteries forming plaque. Eventually this plaque build-up can lead to a narrowing of the arteries.

This narrowing can slow or block blood flow to vital organs such as the heart and brain. This blocking of blood flow can result in a heart attackor stroke.

HDL cholesterol is often called 'good' cholesterol because it helps keep the bad cholesterol from building up in the arteries and protects against heart disease.

Triglycerides

Triglycerides are another form of fat in your blood that may increase your risk for heart disease.

How this medicine works

This medicine reduces elevated total- cholesterol, LDL (bad) cholesterol and triglycerides and increases HDL (good) cholesterol.

This medicine works by decreasing the absorption of cholesterol in the small intestine and by reducing the amount of cholesterol made in the liver.

this medicine does not help you lose weight.

If you have heart disease and a history of heart attack or hospitalisation for unstable angina (chest pain), this medicine reduces the risk of heart attack, stroke, surgery to increase heart blood flow, or hospitalisation for chest pain.

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

This medicine is not addictive.

Use in Children and Adolescents

This medicine is used in children and adolescents (10 to 17 years of age) to treat familial hypercholesterolaemia, a type of high cholesterol that is hereditary (i.e. passed on through families).

This medicine is not recommended for use in children under 10 years of age, as there have been no studies of its effects in this age group.

Your doctor will assess whether this medicine is suitable for your child. Depending on the pubertal development of your child, This medicine may not be suitable for him or her.

Before you take THIS MEDICINE

When you must not take it

Do not take this medicine if:

  • you have an allergy to this medicine or any of the ingredients listed at the end of this leaflet.
    Symptoms of an allergic reaction may include skin rash, itchiness, shortness of breath, swelling of the face, lips, mouth, tongue or throat.
  • you are pregnant or breast feeding.
    This medicine is contraindicated (i.e. should not be used) during pregnancy and breastfeeding. If you take this medicine during pregnancy and breastfeeding, your baby may absorb this medicine and it may affect your baby's normal development causing foetal malformations (birth defects) or irreversible damage.
  • you have active liver disease or repeated blood tests indicating possible liver problems.
  • you have had muscle pain, tenderness or weakness from other medicines used to treat high cholesterol or triglycerides.
  • You are taking certain medicines such as gemfibrozil, ciclosporin, danazol, fusidic acid and strong CYP3A4 inhibitors like itraconazole and ketoconazole. Please see the section "Taking other medicines" in this CMI for more information.
  • 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 this medicine, talk to your doctor.

Before you start to take it

Tell your doctor if:

  1. you are pregnant or intend to become pregnant.
This medicine should not be used during pregnancy.
  1. you are breast-feeding.
This medicine should not be used while breast feeding.
  1. you have unexplained muscle pain, tenderness or weakness not caused by exercise. This is because on rare occasions, muscle problems can be serious, including muscle breakdown resulting in kidney damage that can lead to death.
Your doctor may do a blood test to check for certain muscle problems.
  1. you are Asian.
  2. you are taking niacin or a niacin-containing product.
  3. you have, or have had, any medical conditions, including liver disease or liver problems.
Your doctor will do a blood test to make sure you have no problems with your liver.
  1. you have kidney disease, diabetes or any other medical problems.
  2. you drink alcohol regularly.
  3. you have any allergies to any other medicines or any other substances, such as foods, preservatives or dyes.
  4. you have or have had myasthenia gravis (a disease causing general muscle weakness including in some cases muscles used for breathing) or ocular myasthenia (a disease causing eye muscle weakness) as statins may lead to occurrence of myasthenia or aggravate the condition.

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

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 should not be taken with NNA-Ezetimibe/Simvastatin. These include:

  • nefazodone, used to treat depression
  • medicines containing cobicistat, a drug used in the treatment of HIV infection.
  • protease inhibitors, including indinavir, nelfinavir, ritonavir, saquinavir, used to treat HIV infection
  • certain hepatitis C virus protease inhibitors (such as boceprevir or telaprevir)
  • gemfibrozil, used to treat high cholesterol levels
  • ciclosporin, used to suppress the immune system
  • danazol
  • erythromycin, clarithromycin, telithromycin and fusidic acid, antibiotics used to treat infections
  • ketoconazole, itraconazole, posaconazole and voriconazole used to treat certain fungal infections.

If you are taking any of the above, your doctor may suggest stopping this medicine temporarily or permanently.

Some medicines and this medicine may interfere with each other. These include:

  • Certain hepatitis C antiviral agents, such as elbasvir, or grazoprevir
  • bile acid sequestrants, such as colestyramine, used to lower cholesterol levels.
  • other medicines to lower cholesterol levels, for example, other fibrates, nicotinic acid (also known as niacin).
  • Warfarin, fluindione, or other drugs used to prevent blood clots
  • colchicine, used for gout
  • verapamil, used to treat high blood pressure and angina
  • diltiazem, used to treat angina
  • amiodarone, used to treat irregular heart beat
  • amlodipine, used to treat high blood pressure and angina
  • digoxin, used to treat heart failure
  • lomitapide (a drug used to treat a serious and rare genetic cholesterol condition)
  • daptomycin, a drug used to treat complicated skin and skin structure infections and bacteraemia

These medicines may be affected by this medicine, may affect how well it works, or may increase the risk of side effects with this medicine. You may need different amounts of your medicine, or you may need to take different medicines or take your medicines at different times.

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

You should also tell any doctor who is prescribing a new medication for you that you are taking this medicine.

How to take this medicine

How much to take

Take this medicine only when prescribed by your doctor.

The recommended dose in adults (18 years and over) is one tablet of either 10/10, 10/20, 10/40 or 10/80 tablet once a day, in the evening. Your doctor will adjust your medicine dose depending on your response.

The recommended dose in adolescents (10 to 17 years of age) with familial hypercholesterolaemia is one tablet of either 10/10, 10/20 or 10/40 tablet once a day, in the evening. The maximum recommended dose in adolescents is 10/40 mg.

Because of the increased risk of muscle problems, the 10/80 tablet is only for patients at high risk of heart disease problems who have not yet reached their cholesterol goal on lower doses.

Swallow this medicine with a glass of water.

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

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

When to take it

This medicine should be taken once a day, in the evening. The liver produces its greatest amount of cholesterol when the body is at rest and when there is no dietary intake. For most people this is at night when asleep. Therefore, this medicine is more effective when taken in the evening. A good time would be after your evening meal. However, it does not matter whether you take it before or after food.

However, take this medicine about the same time each day. Taking this medicine at the same time each day will have the best effect. It will also help you remember when to take your dose.

Your doctor may ask you to take this medicine with other cholesterol lowering agents such as bile acid sequestrants.

If you are taking a bile acid sequestrant, such as colestyramine, take this medicine either at least two hours before or four hours after taking the bile acid sequestrant.

How long to take it

This medicine helps lower your cholesterol. It does not cure your condition.

Therefore, you must continue to take it as directed by your doctor if you expect to lower your cholesterol and keep it down.

You may have to take cholesterol lowering medicine for the rest of your life. If you stop taking this medicine, your cholesterol levels may rise again.

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 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 tablet, 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 of this medicine. Do this even if there are no signs of discomfort or poisoning.

While you are using this medicine

Things you must do

If you become pregnant while taking this medicine, stop taking it and tell your doctor immediately.

Have your blood fats checked when your doctor says, to make sure this medicine is working. Even if you are taking medicines to treat high cholesterol, it is important to have your cholesterol measured regularly. You should also know your cholesterol levels and goals.

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

If you are about to have elective surgery, tell your doctor that you are taking this medicine. Your doctor may suggest stopping the tablets a few days before surgery.

Things you must not do

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

Things to be careful of

Avoid drinking large quantities of alcohol. Drinking large quantities of alcohol may increase your chance of this medicine causing liver problems.

Grapefruit juice should be avoided while taking this medicine. Grapefruit juice contains one or more components that alter the metabolism of some medicines, including this medicine.

Be careful driving or operating machinery until you know how this medicine affects you. There have been side effects reported with this medicine that may affect your ability to drive or operate machinery. Individual responses to this medicine may vary.

High cholesterol can be treated in two main ways:

Lifestyle Changes -
this includes a cholesterol-lowering diet, increasing physical activity, and weight management. Ask your doctor for advice before increasing physical activity.

Medicines -
cholesterol-lowering medicines are used together with lifestyle changes to help lower cholesterol.

Side Effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking NNA- Ezetimibe/Simvastatin.

This medicine helps most people with high cholesterol, 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 immediately or go to accident and emergency at your nearest hospital, if you notice any of the following:

  • swelling of the face, lips, mouth, throat or tongue which may cause difficulty in swallowing or breathing.

These are serious side effects. If you have them, you may have had a serious allergic reaction to this medicine. You may need urgent medical attention or hospitalisation. Serious side effects are rare.

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

  • skin rash and hives
  • severe skin problems
  • dark coloured urine
  • light coloured bowel motions
  • joint pain
  • bleeding or bruising more easily than normal
  • steady abdominal pain with nausea and vomiting.
  • weakness in your arms or legs that worsens after periods of activity, double vision or drooping of your eyelids, difficulty swallowing, or shortness of breath (symptoms of myasthenia).

These may be serious side effects. You may need urgent medical attention. Serious side effects are rare.

Liver problems can also occur and may be serious. Your doctor may do blood tests to check your liver

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

  • feel tired or weak
  • loss of appetite
  • upper belly pain
  • dark urine
  • yellowing of the skin or the white of your eyes.

Tell your doctor immediately if you notice the following:

  • unexplained muscle aches, tenderness or weakness, not caused by exercise (in very rare cases this may not go away after stopping this medicine).

This may be a serious side effect. This is because on rare occasions, muscle problems can be serious, including muscle breakdown resulting in kidney damage that can lead to death. You may need urgent medical attention.

The risk of muscle breakdown is greater at higher doses of this medicine, particularly the 10/80 mg dose.

The risk of muscle breakdown is also greater for older patients (65 years of age and older), female patients, patients with kidney problems, and patients with thyroid problems.

Serious 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.

Tell your doctor if you notice any of the following:

  • Headache
  • Nausea
  • Muscle aches
  • Dizziness
  • Feeling tired
  • Cough
  • Stomach irritation
  • Diarrhoea
  • Decreased appetite
  • Hot flush
  • Hypertension
  • Pain

These are the more common side effects of this medicine or of either ezetimibe or simvastatin.

Tell your doctor if you notice any of the following:

  • Depression
  • Tingling or numbness of the hands or feet
  • Trouble sleeping
  • Poor memory
  • Confusion
  • Erectile dysfunction
  • Breathing problems including persistent cough and/or shortness of breath, that may also occur with fatigue, unexplained weight loss or fever.

These are rare side effects of ezetimibe or simvastatin.

In adolescent patients (10 to 17 years of age) there have been no studies longer than 1 year of the effect of taking this medicine on bone development, growth, social and emotional development, or fertility. Do not be alarmed by these lists of possible side effects. You may not experience any of them.

After using this medicine

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 they may not keep well.

Keep this medicine 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 this medicine 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

This medicine comes in four types of tablets:

NNA-Ezetimibe/Simvastatin 10/10
Light tan, mottled, round, biconvex, 6mm tablets with markings “511” on one side.

AUST R 279116.

NNA-Ezetimibe/Simvastatin 10/20
Light tab, mottled, round, biconvex, 8mm tablets with markings “512” on one side.

AUST R 279099.

NNA-Ezetimibe/Simvastatin 10/40
Light tan, mottled, round, biconvex, 10mm tablets with markings “513” on one side.

AUST R 279121.

NNA-Ezetimibe/Simvastatin 10/80
Light tab, mottled, capsule shaped, biconvex, 17.5 x 7.55mm tablets with markings “515” on one side.

AUST R 279123.".

A starter pack of NNA-Ezetimibe/Simvastatin contains 5 or 10 tablets. A trade pack contains 30 tablets.

Ingredients

Each tablet contains both 10 mg ezetimibe and either 10, 20, 40 or 80 mg simvastatin as active ingredients.

This medicine also contains the following:

  • ascorbic acid
  • butylated hydroxyanisole
  • citric acid
  • croscarmellose sodium
  • hypromellose
  • lactose monohydrate
  • magnesium stearate
  • microcrystalline cellulose
  • propyl gallate
  • iron oxide yellow (E172)
  • iron oxide red (E172)
  • iron oxide black (E172)

This medicine does not contain gluten, tartrazine or any other azo dyes.

Supplier

This medicine is distributed in Australia by

Arrotex Pharmaceuticals Pty Ltd
15 - 17 Chapel Street
Cremorne VIC 3121

www.arrotex.com.au

This leaflet was prepared in November 2023.

Published by MIMS January 2024

BRAND INFORMATION

Brand name

NNA-Ezetimibe/Simvastatin

Active ingredient

Ezetimibe + Simvastatin

Schedule

S4

 

1 Name of Medicine

Ezetimibe and simvastatin.

2 Qualitative and Quantitative Composition

NNA-Ezetimibe/Simvastatin is available for oral use as tablets containing 10 mg of ezetimibe, and 10 mg of simvastatin (NNA-Ezetimibe/Simvastatin 10/10), 10 mg of ezetimibe, and 20 mg of simvastatin (NNA-Ezetimibe/Simvastatin 10/20), 10 mg of ezetimibe, and 40 mg of simvastatin (NNA-Ezetimibe/Simvastatin 10/40), or 10 mg of ezetimibe, and 80 mg of simvastatin (NNA-Ezetimibe/Simvastatin 10/80).
Excipient with known effect. Sugars (as lactose).
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

10/10 mg tablets. Light tan, mottled, round, biconvex, 6 mm tablets with markings "511" on one side.
10/20 mg tablets. Light tan, mottled, round, biconvex, 8 mm tablets with markings "512" on one side.
10/40 mg tablets. Light tan, mottled, round, biconvex, 10 mm tablets with markings "513" on one side.
10/80 mg tablets. Light tan, mottled, capsule shaped, biconvex, 17.5 x 7.55 mm tablets with markings "515" on one side.

4 Clinical Particulars

4.9 Overdose

No specific treatment of overdosage with ezetimibe/simvastatin can be recommended. In the event of an overdose, symptomatic and supportive measures should be employed. Co-administration of ezetimibe (1000 mg/kg) and simvastatin (1000 mg/kg) was well-tolerated in acute, oral toxicity studies in mice and rats. No clinical signs of toxicity were observed in these animals. The estimated oral LD50 for both species was ezetimibe ≥ 1000 mg/kg/simvastatin ≥ 1000 mg/kg.
Ezetimibe. In clinical studies, administration of ezetimibe, 50 mg/day to 15 healthy subjects for up to 14 days, or 40 mg/day to 18 patients with primary hypercholesterolemia for up to 56 days was generally well tolerated.
A few cases of overdosage have been reported; most have not been associated with adverse experiences. Reported adverse experiences have not been serious.
Simvastatin. A few cases of overdosage have been reported; the maximum dose taken was 3.6 g. All patients recovered without sequelae.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.3 Preclinical Safety Data

Genotoxicity. Ezetimibe alone or in combination with simvastatin did not cause gene mutation in bacteria or chromosomal damage in human peripheral lymphocytes or bone marrow cells in mice.
Carcinogenicity. Carcinogenicity studies with ezetimibe/simvastatin combinations have not been performed.
Ezetimibe. Two-year dietary studies with ezetimibe alone in mice and rats showed no evidence of carcinogenic potential. The highest ezetimibe dose (500 mg/kg/day) in mice corresponds to exposure levels approximately 4 and ≥ 150 times the adult human exposure for ezetimibe and total ezetimibe, respectively, based on AUC. Exposures in rats at the highest dose (1500 mg/kg/day in males and 500 mg/kg/day in females) correspond to approximately 2 and 14 times the adult human exposure for ezetimibe and total ezetimibe, respectively.
Simvastatin. Carcinogenicity studies have been conducted in mice at oral doses ranging from 1 to 400 mg/kg/day and in rats at doses of 1 to 100 mg/kg/day. Hepatocellular adenomas and carcinomas were observed in both sexes of both species at doses greater than 25 mg/kg/day. Plasma drug levels in rats at this no-effect dose level, expressed as the AUC for enzyme inhibitory activity, were 3 to 11 times greater than those in humans at the maximum recommended dose, whereas serum levels at the no-effect level in mice were similar to those in humans. Additional findings in mice were increased incidences of pulmonary adenomas at doses greater than 25 mg/kg/day, and of Harderian gland adenomas at 400 mg/kg/day. In rats, the incidence of thyroid follicular adenoma was increased in females at doses greater than 5 mg/kg/day and in males at doses greater than 25 mg/kg/day. These thyroid tumours were associated with focal cystic follicular hyperplasia and may be a secondary effect reflective of a simvastatin-mediated enhancement of thyroid hormone clearance by the liver.

6 Pharmaceutical Particulars

6.7 Physicochemical Properties

Ezetimibe. Ezetimibe is a white, crystalline powder that is freely to very soluble in ethanol, methanol, and acetone and practically insoluble in water.
Chemical structure.
https://stagingapi.mims.com/au/public/v2/images/fullchemgif/CSEZETIM.gif Chemical Name: 1-(4-fluorophenyl)-3(R)-[3-(4-fluorophenyl)- 3(S)- hydroxypropyl]-4(S)- (4-hydroxyphenyl)-2-azetidinone.
Chemical Formula: C24H21F2NO3.
Molecular Weight: 409.4.
CAS number. 163222-33-1.
Simvastatin. Simvastatin is a white to off-white, non-hygroscopic, crystalline powder that is practically insoluble in water, and freely soluble in chloroform, methanol and ethanol.
Chemical structure.
https://stagingapi.mims.com/au/public/v2/images/fullchemgif/CSSIMVAS.gif Chemical Name: Simvastatin is (1S, 3R, 7S, 8S, 8aR)-8-[2- [(2R, 4R)-4-Hydroxy-6-oxotetrahydro- 2H-pyran-2-yl] ethyl]-3-7-dimethyl- 1,2,3,7,8,8ahexahydronaphtalen- 1-yl 2,2-dimethylbutonate.
Chemical Formula: C25H38O5.
Molecular Weight: 418.57.
CAS number. 79902-63-9.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Summary Table of Changes

https://stagingapi.mims.com/au/public/v2/images/fulltablegif/NNAEZSST.gif