Oruvail

Oruvail 100 mg Prolonged-Release Capsules, Hard

Ketoprofen 100 mg

Controlled release capsules

Oruvail is recommended in the management of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, acute articular and peri-articular disorders, (bursitis, capsulitis, synovitis, tendinitis), cervical spondylitis, low back pain (strain, lumbago, sciatica, fibrositis), painful musculo-skeletal conditions, acute gout, dysmenorrhoea and control of pain and inflammation following orthopaedic surgery.

Oruvail reduces joint pain and inflammation and facilitates increase in mobility and functional independence. As with other non-steroidal anti-inflammatory agents, it does not cure the underlying disease.

Adults: 100 - 200 mg once daily, depending on patient weight and on severity of symptoms.

Elderly: The elderly are at increased risk of the serious consequences of adverse reactions. If an NSAID is considered necessary, the lowest effective dose should be used and for the shortest possible duration. The patient should be monitored regularly for GI bleeding during NSAID therapy.

Paediatric dosage not established.

Oruvail capsules are for oral administration. To be taken preferably with or after food.

Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms.

Ketoprofen is contraindicated in patients who have a history of hypersensitivity reactions such as bronchospasm, asthmatic attacks, rhinitis, angioedema, urticaria or other allergic-type reactions to ketoprofen, any other ingredients in this medicine, ASA or other NSAIDs. Severe, rarely fatal, anaphylactic reactions have been reported in such patients.

Ketoprofen is contraindicated in patients with hypersensitivity to any of the excipients of the drug.

Ketoprofen is also contraindicated in the third trimester of pregnancy.

Ketoprofen is contraindicated in the following cases:

- Severe heart failure

- active peptic ulcer, or any history of gastrointestinal bleeding, ulceration or perforation

- haemorrhagic diathesis

- severe hepatic insufficiency

- severe renal insufficiency

The use of ketoprofen with concomitant NSAIDs including cyclooxygenase-2 selective inhibitors should be avoided.

Elderly:

Cardiovascular, Renal and Hepatic impairment:

At the start of treatment, renal function must be carefully monitored in patients with heart impairment, heart failure, liver dysfunction, 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 decomposition.

NSAIDs have also been reported to cause nephrotoxicity in various forms and this can lead to interstitial nephritis, nephrotic syndrome and renal failure.

In patients with abnormal liver function tests or with a history of liver disease, transaminase levels should be evaluated periodically, particularly during long-term therapy. Rare cases of jaundice and hepatitis have been described with ketoprofen.

Cardiovascular and cerebrovascular effects

Appropriate monitoring and advice are required for patients with a history of hypertension and/or mild to moderate congestive heart failure as fluid retention and oedema have been reported in association with NSAID therapy.

Clinical trial and epidemiological data suggest that use of some NSAIDs (particularly at high doses and in long-term treatment) may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke). There are insufficient data to exclude such a risk for ketoprofen.

Patients with uncontrolled hypertension, congestive heart failure, established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with ketoprofen after careful consideration. Similar consideration should be made before initiating long-term treatment in patients with risk factors for cardiovascular disease (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking).

Respiratory disorders:

Patients with asthma combined with chronic rhinitis, chronic sinusitis, and/or nasal polyposis have a higher risk of allergy to aspirin and/or NSAIDs than the rest of the population. Administration of this medicinal product can cause asthma attacks or bronchospasm, particularly in subjects allergic to aspirin or NSAIDs.

Gastrointestinal bleeding, ulceration and perforation:

GI bleeding, ulceration or perforation, which can be fatal, has been reported with all NSAIDs at any time during treatment, with or without warning symptoms or a previous history of serious GI events.

The risk of GI bleeding, ulceration or perforation is higher with increasing NSAlD doses, in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation, and in the elderly.). Ketoprofen should not be used in patients with any history of peptic ulceration.

NSAIDs should be given with care to patients with a history of gastrointestinal disease (e.g. ulcerative colitis, Crohn's disease) as these conditions may be exacerbated.

Patients with a history of gastrointestinal toxicity, particularly when elderly, should report any unusual abdominal symptoms (especially GI bleeding), particularly in the initial stages of treatment.

Caution should be advised in patients receiving concomitant medications which could increase the risk of ulceration or bleeding, such as oral corticosteroids, or anticoagulants such as warfarin, selective serotonin-reuptake inhibitors or anti-platelet agents such as aspirin.

When GI bleeding or ulceration occurs in patients receiving ketoprofen, the treatment should be withdrawn.

SLE and mixed connective tissue disease:

In patients with systemic lupus erythematosis (SLE) and mixed connective tissue disorders, there may be an increased risk of aseptic meningitis.

Female fertility:

The use of ketoprofen, as with other NSAIDs, may impair female fertility and is not recommended in women attempting to conceive. In women who have difficulty conceiving or who are undergoing investigation of infertility, withdrawal of ketoprofen should be considered.

Skin reactions:

Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs. 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. Treatment should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.

Infectious disease:

As with other NSAIDs, in the presence of an infectious disease, it should be noted that the anti-inflammatory, analgesic and the antipyretic properties of ketoprofen may mask the usual signs of infection progression such as fever.

Visual disturbances:

If visual disturbances such as blurred vision occur, treatment should be discontinued.

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

The following CIOMS frequency rating is used, when applicable:

Very common (> 1/10); common (> 1/100 to <1/10); uncommon (> 1/1,000 to < 1/100); rare (> 1/10,000 to < 1/1,000); very rare (< 1/10,000), not known (cannot be estimated from the available data).

The following adverse reactions have been reported with Ketoprofen in adults:

Blood and lymphatic system disorders

- rare: haemorrhagic anaemia, anaemia due to bleeding

- not known: agranulocytosis, thrombocytopenia, bone marrow failure, neutropenia

Immune system disorders

- rare: anaphylactic reactions (including shock)

Psychiatric disorders

- not known: mood altered

Nervous system disorders

- uncommon: headache, dizziness, somnolence

- rare: paraesthesia

Eye disorders

- not known: optic neuritis

Ear and labyrinth disorders

- rare: tinnitus

Cardiac disorders

- not known: heart failure, oedema

Vascular disorders

- not known: hypertension, vasodilatation

Respiratory, thoracic and mediastinal disorders

- rare: asthma, asthmatic attack

- not known: bronchospasm (particularly in patients with known hypersensitivity to ASA and other NSAIDs), rhinitis, non-specific allergic reactions, dyspnoea

Gastrointestinal disorders

- common: dyspepsia, nausea, abdominal pain, vomiting

- uncommon: constipation, diarrhoea, flatulence, gastritis

- rare: stomatitis, peptic ulcer

- very rare: pancreatitis (very rare reports of pancreatitis have been noted with NSAIDs)

- not known: exacerbation of colitis and Crohn's disease, gastrointestinal haemorrhage and perforation, gastralgia, melaena, haematemesis

Hepatobiliary disorders

- rare: hepatitis, transaminases increased, elevated serum bilirubin due to hepatitis disorders

- not known: abnormal liver function, jaundice

Skin and subcutaneous disorders

- uncommon: rash, pruritis

- not known: photosensitivity reactions, alopecia, urticaria, angioedema, bullous eruption including Stevens-Johnson syndrome and toxic epidermal necrolysis, exfoliative and bullous dermatoses (including epidermal necrolysis, erythema multiforme), purpura

Renal and urinary disorders

- not known: renal failure acute, tubulointerstitial nephritis, nephritic syndrome, renal function tests abnormal

General disorders and administration site conditions

- uncommon: oedema, fatigue

- not known: headache, taste perversion

Investigations

- rare: weight increased

In all cases of major adverse effects Oruvail should be withdrawn at once.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation 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 via Yellow Card Scheme at: www.mhra.gov.uk/yellowcard

Symptoms

Cases of overdose have been reported with doses up to 2.5 g of ketoprofen. In most instances the symptoms observed have been benign and limited to lethargy, drowsiness, nausea, vomiting and epigastric pain. Headache, rarely diarrhoea, disorientation, excitation, coma, dizziness, tinnitus, fainting, occasionally convulsions may also occur. Adverse effects seen after overdose with propionic acid derivatives such as hypotension, bronchospasm and gastro-intestinal haemorrhage should be anticipated.

In cases of significant poisoning, acute renal failure and liver damage are possible.

If renal failure is present, haemodialysis may be useful to remove circulating medicinal product.

Therapeutic measures:

There are no specific antidotes to ketoprofen overdosages. In cases of suspected massive overdosages, a gastric lavage is recommended and symptomatic and supportive treatment should be instituted to compensate for dehydration, to monitor urinary excretion and to correct acidosis, if present.

Owing to the slow release characteristics of Oruvail, it should be expected that ketoprofen will continue to be absorbed for up to 16 hours after ingestion.

Within one hour of ingestion, consideration should be given to administering activated charcoal in an attempt to reduce absorption of slowly-released ketoprofen.

Alternatively, in adults, gastric lavage, aimed at recovering pellets that may still be in the stomach, should be considered if the patient presents within 1 hour of ingesting a potentially toxic amount.

It should be possible to identify the pellets in the gastric contents. Correction of severe electrolyte abnormalities may need to be considered.

Good urine output should be ensured.

Renal and liver function should be closely monitored.

Patients should be observed for at least four hours after ingestion of potentially toxic amounts.

Frequent or prolonged convulsions should be treated with intravenous diazepam.

The benefit of gastric decontamination is uncertain.

Other measures may be indicated by the patient's clinical condition.

Ketoprofen overall has the properties of a potent non-steroidal anti-inflammatory agent. It has the following pharmacological effects:

Anti-inflammatory

It inhibits the development of carageenan-induced abscesses in rats at 1mg/kg, UV radiation induced erythema in guinea pigs at 6mg/kg. It is also a potent inhibitor of PGE₂ and PFG₂ synthesis in guinea pig and human chopped lung preparations.

Analgesic

Ketoprofen effectively reduced visceral pain in mice caused by phenyl benzoquinone or by bradykinin following p.o. Administration at about 6 mg/kg.

Antipyretic

Ketoprofen (2 and 6 mg/kg) inhibited hyperthermia caused by s.c injection of brewer's yeast in rats and, at 1 mg/kg hyperthermia caused by i.v. administration of anticoagulant vaccine to rabbits.

Ketoprofen at 10 mg/kg i.v. did not affect the cardiovascular, respiratory, central nervous system or autonomic nervous systems.

Ketoprofen is slowly but completely absorbed from Oruvail capsules. Maximum plasma concentration occurs after 6 - 8 hours. It declines thereafter with a half-life of about 8 hours. There is no accumulation on continued daily dosing. Ketoprofen is very highly bound to plasma protein

No additional data of relevance to the prescriber.

Pellets

Sugar spheres

Colloidal anhydrous silica

Shellac

Ethylcellulose

Talc

Capsule shell-body

Gelatin

Erythrosine (E127)

Capsule shell - cap

Gelatin

Titanium dioxide (E171)

Erythrosine (E127)

Patent blue V (E131)

None stated

36 months

Securitainer / HDPE bottle: Store below 30°C in a dry place.

Blister pack: Store below 25°C in a dry place and protect from light.

Securitainer or HDPE bottle containing 100 capsules.

UPVC/Aluminium foil blister or UPVC coated with PVDC aluminium foil blister containing either 8, 28, 30 or 56 capsules

Not all pack sizes may be marketed.

None stated

Aventis Pharma Limited also trading as Aventis Pharma

One Onslow Street

Guildford

Surrey

GU1 4YS

UK

Or trading as

Sanofi-aventis or Sanofi

One Onslow Street

Guildford

Surrey

GU1 4YS

UK

PL 04425/0597

04 September 2006

31 July 2017