Consumer medicine information

Oruvail SR

Ketoprofen

BRAND INFORMATION

Brand name

Oruvail SR

Active ingredient

Ketoprofen

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Oruvail SR.

SUMMARY CMI

Oruvail SR®

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using Oruvail SR?

Oruvail SR contains the active ingredient ketoprofen. Oruvail SR is used to treat the symptoms of rheumatoid arthritis and osteoarthritis. Oruvail SR belongs to a family of medicines called Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). These medicines work by relieving pain and inflammation.

For more information, see Section 1. Why am I using Oruvail SR? in the full CMI.

2. What should I know before I use Oruvail SR?

Do not use if you have ever had an allergic reaction to ketoprofen, aspirin or any other anti-inflammatory drugs, or any of the ingredients listed at the end of the CMI.

Do not use if you have a peptic ulcer; problems with your heart; severe kidney or liver problems.

Do not use if you are in your third trimester of pregnancy.

The use of Oruvail SR during the first and second trimester of pregnancy should be avoided, as the safety of Oruvail SR in pregnant women has not been evaluated.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I use Oruvail SR? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with Oruvail SR and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use Oruvail SR?

  • The usual dose for this medicine is 100mg to 200mg taken once a day, with food and plenty of fluids.
  • Follow the instructions provided and use Oruvail SR until your doctor tells you to stop.

More instructions can be found in Section 4. How do I use Oruvail SR? in the full CMI.

5. What should I know while using Oruvail SR?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are using Oruvail SR.
  • Call your doctor straight away if you become pregnant while you are taking this medicine
  • Call your doctor straight away if you get an infection while taking Oruvail SR
Things you should not do
  • Do not take more than the recommended dose unless your doctor tells you to.
  • Do not take if you have a history of bleeding or ruptured gut, related to previous NSAIDs therapy.
Driving or using machines
  • Be careful before you drive or use any machines or tools until you know how Oruvail SR affects you.
Looking after your medicine
  • Store it in a cool (below 25°C), dry place away from moisture, heat or sunlight.

For more information, see Section 5. What should I know while using Oruvail SR? in the full CMI.

6. Are there any side effects?

There are a number of serious side effects associated with this medicine. It is important to be aware of them so you can identify any symptoms if they occur.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

Oruvail SR®

Active ingredient: Ketoprofen


Consumer Medicine Information (CMI)

This leaflet provides important information about using Oruvail SR. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using Oruvail SR.

Where to find information in this leaflet:

1. Why am I using Oruvail SR?
2. What should I know before I use Oruvail SR?
3. What if I am taking other medicines?
4. How do I take Oruvail SR?
5. What should I know while using Oruvail SR?
6. Are there any side effects?
7. Product details

1. Why am I using Oruvail SR?

Oruvail SR contains the active ingredient ketoprofen. Oruvail SR belongs to a family of medicines called Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). These medicines work by relieving pain and inflammation.

Oruvail SR relieves pain and reduces inflammation (swelling, redness and soreness) that may occur in rheumatoid arthritis or osteoarthritis.

Oruvail SR is used to treat the symptoms of rheumatoid arthritis and osteoarthritis. Although Oruvail SR can relieve the symptoms of pain and inflammation, it will not cure your condition.

2. What should I know before I use Oruvail SR?

Warnings

Do not use Oruvail SR if:

  • you have a peptic ulcer (e.g., a stomach ulcer), or have had peptic ulcers before
  • you have a history of bleeding or ruptured gut, related to previous NSAIDs therapy
  • you have problems with your heart
  • you have severe kidney or liver disease
  • you are in your third trimester of pregnancy
  • you are allergic to aspirin or any other anti-inflammatory medicines.
  • you are allergic to ketoprofen, or any of the ingredients listed at the end of this leaflet.
  • you are in the last 3 months of pregnancy

Some symptoms of an allergic reaction include skin rash, itching, shortness of breath or swelling of the face, lips or tongue, which may cause difficulty in swallowing or breathing.

Always check the ingredients to make sure you can use this medicine.

Do not take Oruvail SR if the packaging is torn or shows signs of tampering.

Check with your doctor if you:

  • have allergies to:
    - any of the ingredients listed at the end of this leaflet
  • have any other medical conditions, especially:
    - heartburn, indigestion, stomach ulcer or other stomach problems
    - bowel or intestinal problems such as ulcerative colitis
    - kidney or liver disease
    - high levels of potassium in your blood
    - eye problems
    - high blood pressure or heart problems
    - swelling of hands, ankles or feet
    - a tendency to bleed or other blood problems
    - asthma or a history of asthma
    - skin problems or a history of skin problems or allergic reaction
  • take any medicines for any other condition
  • plan to have surgery
  • if you are over 65 and unwell or taking other medicines
  • currently have an infection.

If you take Oruvail SR while you have an infection, Oruvail SR may hide some of the signs of an infection such as fever and pain. This may make you think, mistakenly, that you are better or that it is not serious.

It is therefore possible that Oruvail SR may delay appropriate treatment of infection, which may lead to an increased risk of complications. This has been observed in pneumonia caused by bacteria and bacterial skin infections related to chickenpox. If you take this medicine while you have an infection and your symptoms of the infection persist or worsen, consult a doctor without delay.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

  • Do not use if you are in your third trimester of pregnancy.
Taking Oruvail around 20 weeks of pregnancy or later may harm your unborn baby. If you need to take Oruvail for more than 2 days when you are between 20 and 30 weeks of pregnancy, your healthcare provider may need to monitor the amount of fluid in your womb around your baby. You should not take Oruvail after 6 months of pregnancy.
  • The use of Oruvail SR during the first and second trimester of pregnancy should be avoided, as the safety of Oruvail SR in pregnant women has not been evaluated.

It may affect your developing baby if you take it during pregnancy. Like most NSAIDs, Oruvail SR is not recommended to be used during pregnancy. Your doctor will discuss the risks and benefits of taking it if you are pregnant.

  • Do not take it if you are breastfeeding or planning to breastfeed.

Oruvail SR passes into breast milk and there is a possibility your baby may be affected.

Use in children

  • Do not give Oruvail SR to a child or adolescent.

Oruvail SR is not recommended for use in children as there have been no studies of its effects in children.

3. What if I am taking other medicines?

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

Some medicines may interfere with Oruvail SR and affect how it works.

  • aspirin, salicylates or other NSAID eg. Ibuprofen (anti-inflammatory) medicines
  • anticoagulants, sometimes called ‘blood thinners’, such as warfarin, and other medicines used to treat or prevent blood clots
  • medicines used to treat some types of depression or epilepsy (eg. lithium)
  • certain medicines used to treat cancer and arthritis such as methotrexate
  • diuretics, also called fluid or water capsules
  • trimethoprim, a medicine used to prevent or treat urinary tract infections
  • medicines used to treat high blood pressure or various heart conditions
  • probenecid, a medicine used to treat gout
  • pentoxifylline (oxpentifylline), a medicine used to improve the circulation of the blood
  • medicines used to help prevent organ transplant rejection or certain problems with the immune system (eg. ciclosporin, tacrolimus)
  • steroids (eg, corticosteroids such as hydrocortisone)
  • some medicines used to treat depression (eg. SSRIs such as fluoxetine)
  • some medicines used to treat HIV (eg. tenofovir)
  • some contraceptive devices (e.g., intrauterine devices)

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect Oruvail SR.

4. How do I take Oruvail SR?

How much to take

  • The usual dose for this medicine is 100mg to 200mg taken once a day, with food and plenty of fluids.
  • Follow the instructions provided and use Oruvail SR until your doctor tells you to stop.
  • The lowest effective dose should be used for the shortest duration necessary to relieve symptoms.

When to take Oruvail SR

  • Take Oruvail SR at about the same time each day.
  • Depending on your condition, you may need Oruvail SR for a few days, a few weeks or for longer periods.

As with other NSAID medicines, if you are using Oruvail SR for arthritis, it will not cure your condition, but it should help to control pain, swelling and stiffness. If you have arthritis, Oruvail SR should be taken every day for as long as your doctor prescribes.

If you forget to take Oruvail SR

Oruvail SR should be taken regularly at the same time each day.

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

If you miss your dose at the usual time, and if there is still a long time until your next dose, take it as soon as you remember. Then go back to taking it as you would normally.

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

If you take too much Oruvail SR

If you think that you have used too much Oruvail SR, you may need urgent medical attention.

You should immediately:

  • phone the Poisons Information Centre
    (by calling Australia 13 11 26 or New Zealand 0800 POISON or 0800764766), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while using Oruvail SR?

Things you should do

  • Tell all the doctors, dentists and pharmacists who are treating you that you are taking Oruvail SR.
  • If you are about to be started on any new medicine, tell your doctor and pharmacist that you are taking Oruvail SR.
  • If you plan to have surgery that needs a general anaesthetic, tell your doctor or dentist that you are taking this medicine.

Call your doctor straight away if you:

  • become pregnant while you are taking this medicine.
  • get an infection while taking Oruvail SR.

Oruvail SR may hide some of the signs of an infection and may make you think, mistakenly, that you are better or that it is not serious. Signs of an infection may include fever, pain, swelling, redness.

Remind any doctor, dentist or pharmacist you visit that you are using Oruvail SR.

Things you should not do

  • Do not take more than the recommended dose unless your doctor tells you to.
  • Do not give this medicine to anyone else, even if they have the same condition as you.
  • Do not use this medicine to treat any other complaints unless your doctor tells you to.
  • Do not stop taking Oruvail SR, or lower the dosage, without checking with your doctor or pharmacist.
  • Do not stop taking your capsules because you are feeling better, unless advised by your doctor or pharmacist.

Things that may help your condition

Some self-help measures suggested as follows may help your condition.

Talk to your doctor, physiotherapist or pharmacist about them:

  • Weight and diet

Your doctor may suggest losing some weight to reduce the stress on your joints. Eat a healthy diet which includes plenty of fresh vegetables, fruit, bread, cereals and fish. Also eat less fat and sugar.

  • Exercise

Regular exercise may be recommended by your doctor or physiotherapist to help keep or improve movement and strengthen muscles. Before starting any exercise, ask your doctor or physiotherapist about the best kind of program for you.

  • Rest

Rest is important and is usually balanced with exercise and activity. Rest is needed when joints are hot, swollen or painful.

  • Heat

Hot showers or baths may help to ease the pain and relax the muscles that can become tense with arthritis. Your physiotherapist or doctor can prescribe other forms of heat treatment.

  • Physical aids

Are available to help with daily household tasks. For example, there are gadgets and aids to help turn on taps, remove screw tops, pick up objects and handles can be fitted in bathrooms. Ask your doctor to give you information.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how Oruvail SR affects you.

It may cause dizziness or light-headedness in some people, especially after the first dose. Make sure you know how you react to it before you drive a car, operate machinery, or do anything else that could be dangerous if you feel dizzy.

Drinking alcohol

Tell your doctor if you drink alcohol.

Looking after your medicine

Follow the instructions on the carton on how to take care of your medicine properly.

Store in a cool (below 25°C), dry place away from moisture, heat or sunlight; for example, do not store it:

  • in the bathroom or near a sink, or
  • in the car or on window sills.

Keep it where young children cannot reach it.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effectsWhat to do
Gastrointestinal-related
  • stomach upset including nausea (feeling sick), vomiting, heartburn, indigestion, cramps
  • loss of appetite
  • constipation, diarrhoea, pain in the stomach, wind
  • ulcers
Nervous system-related
  • dizziness
  • drowsiness
  • headache
  • disorientation
  • buzzing or ringing in the ears
Skin-related
  • dry or itchy skin
  • rash
  • sore or dry mouth or tongue
Other
  • weight loss
Speak to your doctor or pharmacist if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
Gastrointestinal-related
  • severe pain or tenderness in the stomach
  • vomiting blood or material that looks like coffee grounds
  • bleeding from the back passage, black sticky bowel motions (stools) or bloody diarrhoea
Heart and blood-related:
  • Worsening of heart failure (symptoms of heart failure include shortness of breath, tiring easily after light exercise and swollen ankles & feet).
  • pain or tightness in the chest
  • fast or irregular heartbeats, also called palpitations
  • signs of anaemia, such as tiredness, being short of breath, and looking pale
Kidney and liver-related
  • bleeding or bruising more easily than normal, reddish or purplish blotches under the skin
  • a change in the colour of urine passed, blood in the urine
  • a change in the amount or frequency of urine passed, burning feeling when passing urine
Other
  • hypersensitivity, fever, rash, facial swelling, swollen lymph nodes (which could be symptoms relating to taking Oruvail and associated with raised levels of infection fighting cells (eosinophilia))
  • fever, stiff neck, bright lights hurting the eyes, drowsiness or confusion, and nausea and vomiting
  • eye problems such as blurred vision, sore red eyes, itchy eyes, or fluid build up in the eyelids
  • asthma, wheezing, shortness of breath
  • sudden or severe itching, skin rash, hives
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.
Allergic reaction-related:
  • swelling of the face, lips, mouth or throat, which may cause difficultly in swallowing or breathing
  • hives
  • fainting
Stop taking this medicine and tell your doctor immediately, or go to the Emergency Department at your nearest hospital.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people. If you are over 65 years of age you may have an increased chance of getting side effects.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects as follows:

For Australia: Therapeutic Goods Administration online at: www.tga.gov.au/reporting-problems.

New Zealand: Medsafe online at: www.medsafe.govt.nz/safety/report-a-problem.asp

By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

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

What Oruvail SR contains

Active ingredient
(main ingredient)
ketoprofen
Other ingredients
(inactive ingredients)
colloidal anhydrous silica
shellac
ethylcellulose
purified talc
non-pareil beads (PI 1014) (maize starch, sucrose)
sodium lauryl sulfate
erythrosine
titanium dioxide
gelatin
opacode blue (PI 12300)

Do not take this medicine if you are allergic to any of these ingredients.

What Oruvail SR looks like

Oruvail SR 200mg - are pink and white capsules, containing white pellets marked with "ORUVAIL SR 200".

The 200mg strength is available in boxes of 28 capsules.

Aust R 42422.

Who distributes Oruvail SR

Oruvail SR is supplied in Australia by:

sanofi-aventis australia pty ltd
12-24 Talavera Road
Macquarie Park NSW 2113

Oruvail SR is supplied in New Zealand by:

sanofi-aventis new zealand limited
56 Cawley St, Ellerslie, Auckland
New Zealand

This leaflet was prepared in May 2022.
oruvail-sr-ccdsv12-cmiv6-25may22

Published by MIMS July 2022

BRAND INFORMATION

Brand name

Oruvail SR

Active ingredient

Ketoprofen

Schedule

S4

 

1 Name of Medicine

Ketoprofen.

2 Qualitative and Quantitative Composition

Oruvail SR capsules contain ketoprofen 200 mg.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Hard gelatin capsule, clear pink base and white opaque cap. Base and Cap printed 'ORUVAIL 200' and contains off-white to cream spherical pellets.

4 Clinical Particulars

4.1 Therapeutic Indications

Rheumatoid arthritis, osteoarthritis.

4.2 Dose and Method of Administration

After assessing the risk/ benefit ratio in each individual patient, the lowest effective dose for the shortest possible duration should be used (see Section 4.4 Special Warnings and Precautions for Use). Patients on long-term treatment should be reviewed regularly with regards to efficacy, risk factors and ongoing need for treatment.
100 to 200 mg once daily depending on the patient's weight and on the severity of symptoms. Oruvail SR should be taken with food.

Use in pregnancy.

See Section 4.3 Contraindications; Section 4.6 Fertility, Pregnancy and Lactation.

Use in the elderly.

It is generally advisable in the elderly to begin ketoprofen therapy at the lower end of the dosage range and to maintain such patients on the lowest effective dosage.

4.3 Contraindications

Active or history of gastrointestinal inflammatory disorder or ulceration, haemorrhage, chronic dyspepsia.
History of gastrointestinal bleeding or perforation, related to previous NSAID therapy.
Known hypersensitivity to ketoprofen, aspirin or other NSAIDs.
Patients in whom aspirin or other NSAIDs induce symptoms of asthma, rhinitis or urticaria. Severe, rarely fatal anaphylactic reactions have been reported in such patients.
Third trimester of pregnancy (see Section 4.6 Fertility, Pregnancy and Lactation).
Severe heart failure.
Severe renal insufficiency.
Severe hepatic impairment.
Treatment of perioperative pain in setting of coronary artery bypass surgery (CABG).

4.4 Special Warnings and Precautions for Use

Cardiovascular thrombotic events.

Observational studies have shown that nonselective NSAIDs may be associated with an increased risk of serious CV events including myocardial infarction, stroke and heart failure, which may increase with dose or duration of use. Additionally patients with CV disease, history of atherosclerotic CV disease or risk factors for CV disease may be at greater risk. However, to minimise the potential risk of an adverse CV event, especially in patients with CV risk factors, the lowest effective dose should be used for the shortest possible duration. There is no consistent evidence to suggest that concurrent use of aspirin mitigates the increased risk of serious CV events associated with NSAID use.
Physicians and patients should remain alert for such CV events, even in the absence of previous CV symptoms. Patients should be informed about signs and/or symptoms of serious CV toxicity and the steps to take if they occur.
An increased risk for arterial thrombotic events has been reported in patients treated with non-aspirin NSAIDs for perioperative pain in the setting of coronary artery bypass surgery (see Section 4.3 Contraindications).

Hypertension.

NSAIDs can lead to onset of new hypertension or worsening of pre-existing hypertension. Patients taking antihypertensives along with NSAIDs may have an impaired antihypertensive response and hence NSAIDs should be administered with caution in patients with hypertension. Furthermore, when given to patients with hypertension, blood pressure should be monitored closely during initiation of NSAID treatment and at regular intervals thereafter.
Increased risk of atrial fibrillation has been reported in association with the use of NSAIDs.

Heart failure.

Fluid retention and oedema have been observed in some patients taking NSAIDs and NSAIDs should be used with caution in patients with fluid retention or heart failure.

Gastrointestinal events.

All NSAIDs can cause GI discomfort and serious, potentially fatal GI effects such as ulcers, bleeding and perforation which may increase with dose or duration of use, but can occur at any time without warning. Upper GI ulcers, gross bleeding or perforation caused by NSAIDs occur in approximately 1% of patients treated for 3-6 months and in about 2-4% of patients treated for one year. These trends continue with longer duration of use, increasing the likelihood of developing a serious GI event at some time during the course of therapy. However, even short-term therapy is not without risk.
Due to the possibility of severe gastrointestinal lesions, particular attention should be paid to any digestive disturbance and especially to gastrointestinal bleeding. This risk is especially high in patients who continue to receive anticoagulant therapy. Elderly patients are at greater risk for serious GI events. Other risk factors associated with increased risk of developing serious GI events include history of serious GI events, smoking and alcoholism. When gastrointestinal bleeding or ulcerations occur in patients receiving NSAIDs, the medicine should be withdrawn immediately. Doctors should warn patients about the signs and symptoms of serious GI toxicity and what steps to take if they occur. The risk of serious GI events associated with ketoprofen ranged from 0.03 to 1.7% with a higher incidence in elderly.
The concurrent use of NSAIDs and aspirin does increase the risk of serious GI events.
Caution should be advised in patients receiving concomitant medications which could increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors, nicorandil or antiplatelet agents such as aspirin (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Because serious GI tract ulceration and bleeding can occur without warning symptoms, physicians should follow chronically treated patients for the signs and symptoms of ulceration and bleeding and should inform them of the importance of this follow-up.

Serious skin reactions.

NSAIDs may very rarely cause serious cutaneous adverse events such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome (see Drug Reaction with Eosinophilia with Systemic Symptoms (DRESS)), which can be fatal and occur without warning. These serious adverse events are idiosyncratic and are independent of dose or duration of use. Patients appear to be at highest risk of these reactions early in the course of therapy, the onset of the reaction occurring in the majority of cases within the first month of treatment. Patients should be advised of the signs and symptoms of serious skin reactions and to consult their doctor at the first appearance of skin rash or any signs of hypersensitivity.

Drug reaction with eosinophilia with systemic symptoms (DRESS).

DRESS has been reported in patients using NSAIDs. Some of these events have been fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling. Other clinical manifestations may include hepatitis, nephritis, haematological abnormalities, myocarditis, or myositis. Sometimes symptoms of DRESS may resemble an acute viral infection. Eosinophilia is often present. Because this disorder is variable in its presentation, other organ systems not noted here may be involved. It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. If such signs or symptoms are present, discontinue the NSAID and evaluate the patient immediately.

Steroid therapy.

Withdrawal of concomitant steroid therapy.

It is recommended that if steroids are reduced or discontinued during ketoprofen therapy, the dose should be reduced slowly and the patients should be monitored closely for adverse effects, particularly adrenal insufficiency and exacerbation of the symptoms of rheumatoid arthritis.

Infection.

Masking of symptoms of underlying infections.
Oruvail SR can mask symptoms of infection, which may lead to delayed initiation of appropriate treatment and thereby worsening the outcome of the infection. This has been observed in bacterial community acquired pneumonia and bacterial complications to varicella. When Oruvail SR is administered for fever or pain relief in relation to infection, monitoring of infection is advised. In non-hospital settings, the patient should consult a doctor if symptoms persist or worsen.

Haematology.

There have been sporadic reports of decreased haematocrit and haemoglobin values without progressive deterioration on prolonged administration of the medicine. Anaemia is commonly observed in rheumatoid arthritis patients and is sometimes aggravated by nonsteroidal anti-inflammatory medicines which may produce fluid retention or significant gastrointestinal blood loss in some patients. Patients on long-term treatment with NSAIDs, including ketoprofen, should have their haemoglobin or haematocrit checked if they develop signs or symptoms of anaemia.

Hyperkalaemia.

Hyperkalaemia may occur, especially in patients with underlying diabetes, renal failure, and/or concomitant treatment with hyperkalaemia promoting agents. Potassium levels must be monitored under these circumstances (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Ophthalmological effects.

Adverse ophthalmological effects have been observed with nonsteroidal anti-inflammatory agents; accordingly, in patients who develop visual disturbances during treatment with Oruvail, treatment should be discontinued pending a complete ophthalmological examination.

Oligohydramnios/neonatal renal impairment.

Use of NSAIDs, including Oruvail, from about 20 weeks gestation or later in pregnancy may cause fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. These adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after NSAID initiation.
Oligohydramnios is often, but not always, reversible with treatment discontinuation. Complications of prolonged oligohydramnios may, for example, include limb contractures and delayed lung maturation. In some postmarketing cases of impaired neonatal renal function, invasive procedures such as exchange transfusion or dialysis were required.
If NSAID treatment is necessary between about 20 weeks and 30 weeks gestation, it should be managed under medical supervision and limit Oruvail use to the lowest effective dose and shortest duration possible. Consider ultrasound monitoring of amniotic fluid if Oruvail treatment extends beyond 48 hours. Discontinue Oruvail if oligohydramnios occurs and follow up according to clinical practice (see Section 4.6 Fertility, Pregnancy and Lactation).

Use in hepatic impairment.

Impaired hepatic function.

Serious hepatic adverse events appear to be rare with ketoprofen. Rare cases of jaundice and hepatitis have been described with ketoprofen. As with other NSAIDs abnormal liver function test (such as elevation of AST, ALT and SAP) may occur in up to 15% of patients. These abnormalities may progress, may remain essentially unchanged, or may resolve with continued therapy. Meaningful elevations (three times the upper limit of normal) of ALT or AST occurred in controlled clinical trials in less than 1% of patients.
Physicians and patients should remain alert for the hepatotoxicity. Patients should be informed about the signs and/or symptoms of hepatotoxicity (e.g. nausea, fatigue, lethargy, pruritus, jaundice, abdominal tenderness in the right upper quadrant and flu-like symptoms) and the steps to take should these signs and/or symptoms occur. If an abnormal liver function test occurs, it should be monitored until it returns to normal. If a significant abnormality persists, ketoprofen should be discontinued. It is recommended that in those patients with a history of liver dysfunction periodic liver function test be carried out.

Plasma protein binding medicines.

Ketoprofen is highly protein bound. Concomitant use of other protein binding medicines, e.g. anticoagulants, sulphonamides, hydantoins, might necessitate modification of dosage in order to avoid increased levels of such medicines resulting from competition for protein binding sites.

Use in renal impairment.

Inhibition of renal prostaglandin synthesis by NSAIDs may interfere with renal function, especially in the presence of existing renal disease. As with other NSAIDs, ketoprofen should be used with caution in patients with renal impairment. At the start of treatment and periodically, renal function must be carefully monitored in patients with heart failure, cirrhosis and nephrosis, in patients receiving diuretic therapy, in patients with chronic renal impairment, particularly if the patient is elderly. In these patients, administration of ketoprofen may induce a reduction in renal blood flow caused by prostaglandin inhibition and lead to renal decompensation. Abnormalities in LDH and BUN have occurred in patients on ketoprofen therapy.

Use in the elderly.

In pharmacokinetic studies, ketoprofen clearance was reduced in older patients receiving ketoprofen compared with younger patients. Peak ketoprofen concentrations and free drug AUC were increased in older patients. The glucuronide conjugate of ketoprofen, which can serve as a potential reservoir for the parent drug, is known to be substantially excreted by the kidney. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection. It is recommended that the initial dosage of ketoprofen should be reduced for patients over 75 years of age and it may be useful to monitor renal function. In addition, the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Elderly patients may be more sensitive to the antiprostaglandin effects of NSAIDs (on the gastrointestinal tract and kidneys) than younger patients. In particular, elderly or debilitated patients who receive NSAID therapy seem to tolerate gastrointestinal ulceration or bleeding less well than other individuals, and most spontaneous reports of fatal GI events are in this population. Therefore, caution should be exercised in treating the elderly and, when individualising their dosage, extra care should be taken when increasing the dose.
See Section 4.2 Dose and Method of Administration.

Paediatric use.

Ketoprofen is not recommended for children under 12 years since safety and efficacy in this age group have not been established.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

The following interactions have been studied using conventional ketoprofen at a dose of 200 mg daily.

Medicinal products that can promote hyperkalaemia.

The risk of hyperkalaemia can be enhanced when ketoprofen is administered concomitantly with potassium salts, potassium sparing diuretics, ACE inhibitors and angiotensin II antagonists, NSAIDs, heparins (low molecular weight or unfractioned), ciclosporin, tacrolimus and trimethoprim (see Section 4.4 Special Warnings and Precautions for Use).

Antacids.

Concomitant administration of magnesium hydroxide and aluminium hydroxide hydrate does not interfere with the rate or extent of the absorption of ketoprofen.

NSAIDs (including cyclooxygenase-2 selective inhibitors) and high dose salicylates (e.g. aspirin).

Ketoprofen may present an additive effect with other NSAIDs (increased risk of gastrointestinal ulcer and/or haemorrhage). Therefore, concomitant administration is not advised.
Ketoprofen does not alter aspirin absorption. However, in a study of 12 normal subjects, concurrent administration of aspirin decreased ketoprofen protein binding and increased ketoprofen plasma clearance from 0.07 L/kg/hour without aspirin to 0.11 L/kg/hour with aspirin. The clinical significance of these changes has not been adequately studied. Therefore, concurrent use of aspirin and ketoprofen is not recommended.

Diuretics.

Hydrochlorothiazide given concomitantly with ketoprofen produces a reduction in urinary potassium and chloride excretion compared to hydrochlorothiazide alone. Patients and particularly dehydrated patients, taking diuretics are at greater risk of developing renal failure secondary to a decrease in renal blood flow caused by prostaglandin inhibition. Such patients should be rehydrated before initiating coadministration therapy and renal function monitored when the treatment is started.

Digoxin.

In a study of 12 patients with congestive heart failure where ketoprofen and digoxin were concomitantly administered, ketoprofen did not alter the serum levels of digoxin. However, caution is advised, in particular in patients with renal impairment, since NSAIDs may reduce renal function and decrease renal clearance of cardiac glycosides.

Lithium.

There is a risk of elevation of plasma lithium levels, sometimes reaching toxic levels, due to decreased lithium renal excretion. Where necessary, plasma lithium levels should be closely monitored and the lithium dosage levels adjusted during and after NSAIDs therapy.

Parenteral heparin and platelet aggregation inhibitors (i.e. ticlopidine, clopidogrel).

Increased risk of bleeding. If concomitant use is unavoidable, patient should be closely monitored including laboratory test results (bleeding time).

Thrombin inhibitors (such as dabigatran), direct factor Xa inhibitors (such as apixaban, rivaroxaban).

Increased risk of bleeding. If coadministration is unavoidable, patient should be closely monitored.

Vitamin K antagonists (such as warfarin).

Concurrent use of NSAIDs and warfarin has been associated with severe, sometimes fatal, haemorrhage. The exact mechanism of the interaction between NSAIDs and warfarin is unknown, but may involve enhanced bleeding from NSAID induced gastrointestinal ulceration, or an additive effect of anticoagulation by warfarin and inhibition of platelet function by NSAIDs. Ketoprofen should be used in combination with warfarin only if absolutely necessary and patients taking this combination of medicines should be closely monitored.

Probenecid.

Probenecid increases both free and bound ketoprofen through reducing the plasma clearance of ketoprofen to about one-third as well as decreasing its protein binding. Therefore, the combination of ketoprofen and probenecid is not recommended.

Methotrexate.

Methotrexate at doses greater than 15 mg/week.

Methotrexate is highly protein bound and may be displaced by NSAIDs including ketoprofen. Concomitant administration of some NSAIDs with high dose methotrexate therapy has been reported to elevate and prolong serum methotrexate levels, resulting in severe haematologic and gastrointestinal toxicity which may lead to death.

Methotrexate at doses lower than 15 mg/week.

During the first weeks of combination treatment, full blood count should be monitored weekly. If there is any alteration of the renal function, or if patient is elderly, monitoring should be more frequent.

Ciclosporin and tacrolimus.

There is increased risk of nephrotoxicity.

Pentoxifylline (oxpentifylline).

There is an increased risk of bleeding. More frequent clinical monitoring and monitoring of bleeding time is required.

Tenofovir.

Concomitant administration of tenofovir disoproxil fumarate and NSAIDs may increase the risk of renal failure.

Nicorandil.

In patients concomitantly receiving nicorandil and NSAIDs, there is an increased risk for severe complications such as gastrointestinal ulceration, perforation and haemorrhage (see Section 4.4 Special Warnings and Precautions for Use, Gastrointestinal events).

Antihypertensive agents (beta-blockers, angiotensin converting enzyme inhibitors, diuretics).

Risk of decrease in antihypertensive potency (inhibition of vasodilator prostaglandins by NSAIDs).

ACE inhibitors and angiotensin II antagonists.

In patients with compromised renal function (e.g. dehydrated patients or elderly patients), the coadministration of an ACE inhibitor or angiotensin II antagonist and agents that inhibit cyclooxygenase may result in further deterioration of renal function, including possible acute renal failure.

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

Concomitant use of a renin angiotensin system inhibiting medicine (ACE inhibitor or angiotensin receptor antagonist), an anti-inflammatory medicine (NSAID, including COX-2 inhibitor) and a thiazide diuretic may increase the risk of renal impairment. This includes use in fixed combination products containing more than one class of medicine. The combination of these agents should be administered with caution, especially in the elderly and in patients with pre-existing renal impairment. Renal function (serum creatinine) should be monitored after initiation of concomitant therapy, and periodically thereafter.

Thrombolytics.

There is an increased risk of bleeding.

Gemeprost.

The efficacy of gemeprost may be reduced.

IUD.

The efficacy of IUDs may be reduced and result in a pregnancy.

Corticosteroids.

Increased risk of gastrointestinal ulceration or bleeding (see Section 4.4 Special Warnings and Precautions for Use, Gastrointestinal events).

Selective serotonin reuptake inhibitors (SSRIs).

Increased risk of gastrointestinal bleeding (see Section 4.4 Special Warnings and Precautions for Use, Gastrointestinal events).

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category C)
Pregnancy Category C - Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing, harmful effects on the human fetus or neonate without causing malformations. These effects may be reversible. Accompanying texts should be consulted for further details.
The use of NSAIDs may impair female fertility and is not recommended in women attempting to conceive. In women who have difficulties conceiving or who are undergoing investigation of infertility, withdrawal of the NSAID should be considered.
Data from epidemiological studies suggest an increased risk of miscarriage after the use of a prostaglandin synthesis inhibitor in early pregnancy.
Use of NSAIDs, including Oruvail, from about 20 weeks gestation or later in pregnancy has been associated with cases of fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment (see Section 4.4 Special Warnings and Precautions for Use).

During the first and second trimester.

In mice and rats there is no evidence of teratogenic or embryotoxicity. In the rabbit slight embryotoxicity likely related to maternal toxicity has been reported. As the safety of ketoprofen in pregnant women has not been evaluated, the use of ketoprofen during the first and second trimester of pregnancy should be avoided.

During the third trimester of pregnancy.

NSAIDs have an inhibitory effect on prostaglandin synthesis and, when given during the latter part of pregnancy, may cause cardiopulmonary (closure of the fetal ductus arteriosus) and renal toxicity. When given at term, they prolong labour and delay parturition and prolonged bleeding time in both mother and child may occur. Therefore, ketoprofen is contraindicated during the last trimester of pregnancy.
No data are available on excretion of ketoprofen in human milk. In rats, ketoprofen at doses of 9 mg/kg (54 mg/m2/day; approximately 0.3 times the maximum recommended human therapeutic dose) did not affect perinatal development. Upon administration to lactating dogs, the milk concentration of ketoprofen was found to be 4 to 5% of the plasma drug level. As with other medicines that are excreted in milk, ketoprofen is not recommended for use in nursing mothers.

4.7 Effects on Ability to Drive and Use Machines

Patients should be warned about the potential for somnolence, dizziness or convulsions, and advised not to drive or operate machinery if these symptoms occur.

4.8 Adverse Effects (Undesirable Effects)

The following adverse events have been observed with ketoprofen.

More common reactions.

(Incidence greater than 1%.)

Gastrointestinal.

Dyspepsia (11.5%), nausea, abdominal pain, diarrhoea, constipation, flatulence, anorexia, vomiting, stomatitis, gastralgia.

Central nervous system.

Headache, dizziness, CNS inhibition or excitation.

Special senses.

Tinnitus, visual disturbance.

Dermatological.

Rash.

Urogenital.

Impairment of renal function (oedema, increased BUN)*, signs or symptoms of urinary tract irritation.
* Incidence greater than 3%.

Less common reactions.

(Incidence less than 1%.)

Gastrointestinal.

Appetite increase, dry mouth, eructation, gastralgia, dyspepsia, abdominal pain, nausea, vomiting, diarrhoea, constipation, flatulence, gastritis, stomatitis, rectal haemorrhage, melaena, faecal occult blood, salivation, peptic ulcer, gastrointestinal perforation, haematemesis, intestinal ulceration, gastrointestinal bleeding, exacerbation of colitis and Crohn's disease, pancreatitis.

Central nervous system.

Amnesia, confusion, impotence, migraine, paraesthesia, vertigo, fatigue, tension, anxiety, drowsiness, convulsions, depression, hallucinations, aseptic meningitis, mood disorder.
Aseptic meningitis has been reported as a potential rare adverse effect from the administration of several anti-inflammatory medications, including selective and nonselective COX inhibitors.

Special senses.

Conjunctivitis, conjunctivitis sicca, eye pain, hearing impairment, retinal haemorrhage and pigmentation change, taste perversion.

Dermatological.

Alopecia, eczema, pruritus, purpuric rash, sweating, urticaria, angioedema, bullous rash including Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis, photosensitivity discolouration, onycholysis, flushing, acute generalised exanthematous pustulosis.

Body as a whole.

Chills, oedema, pain, allergic reaction, anaphylactic reactions (including shock).

Cardiovascular.

Hypertension, palpitation, tachycardia, congestive heart failure, peripheral vascular disease, vasodilation, vasculitis (including leukocytoclastic vasculitis), bruising, exacerbation of heart failure, atrial fibrillation.

Haematological.

Hypocoagulability, agranulocytosis, anaemia, haemolysis, purpura, thrombocytopenia, bone marrow aplasia, haemolytic anaemia, leucopenia.

Metabolic and nutritional.

Thirst, weight gain, weight loss, hepatic dysfunction, hyponatraemia, hyperkalaemia, elevations of transaminase levels, rare cases of hepatitis.

Mouth.

Mouth ulcers, sore tongue, inflammation of the mouth and gum have been reported.

Infections and infestations.

Oruvail SR can mask symptoms of infection, which may lead to delayed initiation of appropriate treatment and thereby worsening the outcome of infection (including bacterial community-acquired pneumonia and bacterial complications to varicella (see Section 4.4 Special Warnings and Precautions for Use).

Musculoskeletal.

Myalgia.

Respiratory.

Dyspnoea, haemoptysis, epistaxis, pharyngitis, rhinitis, bronchospasm (particularly in patients with hypersensitivity to aspirin and other NSAIDs), laryngeal oedema, asthma.

Urogenital.

Menometrorrhagia, haematuria, renal failure, abnormal renal function tests, interstitial nephritis, nephrotic syndrome.

Hypersensitivity reactions.

Dermatological reactions, rash, pruritus, urticaria, angioedema.

Post marketing experience.

Pregnancy, puerperium and perinatal conditions.

Unknown: oligohydramnios, neonatal renal impairment.

Skin and subcutaneous tissue disorders.

Unknown: Drug Reaction with Eosinophilia with Systemic Symptoms (DRESS).

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

Signs and symptoms following acute NSAID overdose are usually limited to lethargy, drowsiness, abdominal pain, nausea and vomiting which are generally reversible with supportive care. Respiratory depression, coma or convulsions have occurred following large ketoprofen overdoses. Gastrointestinal bleeding, hypotension, hypertension, or acute renal failure may occur but are rare.
Patients should be managed by symptomatic and supportive care following an NSAID overdose. There are no specific antidotes. Gut decontamination may be indicated in patients with symptoms seen within 4 hours (longer for sustained release products) or following a large overdose (5 to 10 times the usual dose). Administration of activated charcoal in an attempt to reduce absorption of ketoprofen should be considered. Forced diuresis, alkalinisation of the urine, haemodialysis or haemoperfusion would probably not be useful due to ketoprofen's high protein binding.
Owing to the sustained release characteristics of Oruvail SR it should be expected that ketoprofen will continue to be absorbed for up to 16 hours after ingestion.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Non-steroidal anti-inflammatory and antirheumatic products, propionic acid derivatives, ATC code: M01AE03.

Mechanism of action.

Animal pharmacological studies have shown that ketoprofen has anti-inflammatory, analgesic and antipyretic properties. It also inhibits prostaglandin synthetase. Ketoprofen has been shown to possess antibradykinin activity in guinea pigs and mice. Inhibition of platelet aggregation has been demonstrated in rabbits.
Ketoprofen reduces joint pain and inflammation and facilitates increase in mobility and functional independence. As with other NSAIDs, it does not cure the underlying disease.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

The sustained release form of ketoprofen is based upon a multiple pellet system, each pellet acting as an individual delivery system bounded by a pH sensitive dialysing membrane which prevents release of ketoprofen in the stomach. About 100 pellets are needed to deliver each 100 mg of ketoprofen.
Owing to gradual release of ketoprofen, maximum plasma concentrations occur around 6 hours after administration of a single dose of 200 mg of ketoprofen. These are considerably lower (3.5 + 1 microgram/mL) than those after a single dose of 100 mg of conventional ketoprofen (10 microgram/mL). The release characteristics of Oruvail SR result in an apparent elimination half-life of 8.4 hours.
There is some evidence that a heavy meal delays the absorption of ketoprofen from the sustained release formulation. However, the bioavailability of the product is unaffected.
Ketoprofen is eliminated by hepatic metabolism as an ester glucuronide conjugate; a minor pathway being aromatic hydroxylation, the resulting inactive metabolites being excreted by the kidney.
Peak plasma concentration of ketoprofen were higher (5 microgram/mL) and occurred later (10.1 hours) in elderly population (mean age 81) than in young healthy subjects (4.2 microgram/mL, 5.6 hours). The apparent elimination half-life was not significantly altered.
In a study using conventional ketoprofen, a decrease in ketoprofen conjugates and reduction in ketoprofen clearance was reported in elderly subjects (mean age 86.3 years).
Accumulation does not occur upon repeated administration of full adult doses of 200 mg/day provided there is no severe impairment of renal or hepatic function.
Severe impairment of renal function may result in impairment of excretion of conjugated ketoprofen and possible consequent regeneration of free ketoprofen from the conjugate.
Ketoprofen is highly protein bound.

Elderly: clearance and unbound fraction.

The plasma and renal clearance of ketoprofen is reduced in the elderly (mean age 73 years) compared to a younger normal population (mean age 27 years). Hence, ketoprofen peak concentration and AUC increase with increasing age. Data from one trial suggest that the increase is greater in women than in men. It has not been determined whether age related changes in absorption among the elderly contribute to the changes in bioavailability of ketoprofen (see Section 4.4 Special Warnings and Precautions for Use, Use in the elderly).

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Erythrosine, ethylcellulose, gelatin, nonpareil beads (PI 1014), Opacode Blue (PI 12300), shellac, colloidal anhydrous silica, sodium lauryl sulfate, purified talc and titanium dioxide.

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 in a dry place.

6.5 Nature and Contents of Container

Oruvail SR 200 mg Capsules (pink/white, containing white pellets, marked ORUVAIL SR 200) are available in a blister pack of 28 capsules.

6.6 Special Precautions for Disposal

In Australia, any unused product or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Ketoprofen is DL-2-(3-benzoylphenyl) propionic acid. It is a white or off white powder with a melting point of about 93°C. MW: 254.3. Ketoprofen is very slightly soluble in water at 20°C, 2% soluble in dimethylformide and readily soluble in benzene, ethanol, chloroform, acetone and ethyl acetate at 20°C.

Chemical structure.


CAS number.

22071-15-4.

7 Medicine Schedule (Poisons Standard)

Prescription Medicine (Schedule 4).

Summary Table of Changes