Austell Diclofenac Sodium Injection

AUSTELL DICLOFENAC 25 mg/mL Injection (75 mg/3 mL Ampoule) Use for intramuscular injection only: For initial therapy of inflammatory and degenerative rheumatic diseases, as well as the treatment of mild to moderately painful conditions due to inflammation of non u2013 rheumatic origin.

Posology

Adults

The maximum total daily dose of AUSTELL DICLOFENAC SODIUM 25 mg/mL by any route is 150 mg.

Paediatric population

Because of the dosage strength, AUSTELL DICLOFENAC is not suitable for use in children and adolescents below 14 years of age (see section 4.3).

Method of administration

Adults

AUSTELL DICLOFENAC should not be given as an intravascular injection. Intramuscular injection AUSTELL DICLOFENAC is given by deep intra-muscular injection into the gluteal muscle in a dose of 75 mg once daily or, if required in severe conditions, 75 mg twice daily. The directions for intramuscular injection must be followed in order to avoid damage to a nerve or other tissues at the injection site. After inserting the needle the plunger should be pulled back to avoid inadvertent intra-arterial injection. Each injection to be given at a different site. Use the lowest effective dose for the shortest possible duration of treatment. AUSTELL DICLOFENAC should not be given for more than 2 days, if necessary, the treatment can be continued with oral or rectal formulation.

• AUSTELL DICLOFENAC is contraindicated in patients with hypersensitivity to diclofenac sodium or any of the other ingredients (see section 6.1).
• AUSTELL DICLOFENAC is also contraindicated in patients in whom attacks of asthma, urticaria, angioedema, heart failure or rhinitis are precipitated by acetylsalicylic acid or by other NSAIDs.
• AUSTELL DICLOFENAC should not be given to patients with gastric or intestinal ulcers, bleeding or perforation.
• AUSTELL DICLOFENAC is contraindicated in patient with a history of gastro-intestinal bleeding, ulceration or perforation (PUBs) related to previous NSAIDs.
• AUSTELL-DICLOFENAC is contraindicated in patients with active or history of recurrent ulcer/haemorrhage/perforations.
• AUSTELL DICLOFENAC is contraindicated in patients with bleeding disorders.
• AUSTELL DICLOFENAC is not recommended for children (see section 4.2).
• Pregnant women from around 20 weeks of gestation or later in pregnancy (see section 4.4 and 4.6).
• Lactation (see section 4.6)
• AUSTELL DICLOFENAC should not be used in patients with porphyria.

General

Strict accuracy of diagnosis and close medical surveillance are imperative in patients with symptoms indicative of gastro-intestinal disease, a case history suggestive of gastro-intestinal ulceration, ulcerative colitis, Crohnu2019s disease, in patients suffering from impaired hepatic function and pre-existing dyshaemopoiesis or disorders of blood coagulation.

Patients undergoing therapy may need to be monitored for development of blood, kidney, liver or eye disorders. Diclofenac may mask the signs and symptoms of infection due to its pharmacodynamic properties.

Renal impairment

AUSTELL DICLOFENAC should be administered with caution to patients with renal impairment. Renal papillary necrosis and nephritic syndrome have been reported in patients taking diclofenac.

Hepatic effects

AUSTELL DICLOFENAC should also be administered with caution in patients with hepatic impairment. Increase of serum aminotransferase activity, clinical hepatitis, including fatal fulminant hepatitis have been reported. Patients using AUSTELL DICLOFENAC for osteoarthritis are at a risk of hepatotoxicity.

Cardiovascular effects

Caution is required in patients with a history of hypertension and/or heart failure as fluid retention and oedema have been reported in association with AUSTELL DICLOFENAC therapy.

Elderly :

The elderly have an increased frequency of adverse reactions to NSAIDs, especially gastro-intestinal bleeding and perforation (PUBs) which may be fatal. AUSTELL DICLOFENAC should be used with caution in the elderly, and AUSTELL DICLOFENAC may have to be given in reduced doses in such patients.

Gastrointestinal effects

The risk of gastro-intestinal bleeding or perforation (PUBs) is higher with increasing doses of AUSTELL DICLOFENAC, in patients with a history of ulcers, and the elderly. When gastro-intestinal bleeding or ulceration occurs in patients receiving AUSTELL DICLOFENAC, treatment with AUSTELL DICLOFENAC should be stopped. AUSTELL DICLOFENAC should be given with caution to patients with a history of gastro-intestinal disease (e.g. ulcerative colitis, Crohnu2019s disease, hiatus hernia, gastro-oesophageal reflux disease, angiodysplasia) as the condition may be exacerbated.

Skin effects

Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported. AUSTELL DICLOFENAC should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity. Also refer to DRESS syndrome below.

Drug Reaction with Eosinophillia and Systemic Symptoms (DRESS) DRESS has been reported in patients taking NSAIDs such as AUSTELL DICLOFENAC. 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. Eosinophillia 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 AUSTELL DICLOFENAC and evaluate the patient immediately.

Risk of foetal renal dysfunction and foetal ductus arteriosus

The use of nonsteroidal anti-inflammatory drugs (NSAIDs) around 20 weeks gestation or later in pregnancy may cause foetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. Oligohydramnios is often, but not always, reversible with treatment discontinuation. Complications of prolonged oligohydramnios may include limb contractures and delayed lung maturation (see section 4.3 and 4.6). Invasive procedures such as exchange transfusion or dialysis may be required. If NSAID treatment is deemed necessary between 20 to 30 weeks of pregnancy, limit use to the lowest effective dose and shortest duration possible. Consider ultrasound monitoring of amniotic fluid if NSAID treatment extends beyond 48 hours. Discontinue the NSAID if oligohydramnios occurs and follow up according to clinical practice (see section 4.3 and 4.6). Avoid prescribing NSAIDs at 30 weeks and later in pregnancy because of the additional risk of premature closure of the foetal ductus arteriosus (see section 4.6).

Lithium or digoxin

When given together with preparations containing lithium or digoxin, AUSTELL DICLOFENAC may raise their plasma concentrations.

Corticosteroids or other NSAIDs

Concomitant administration of glucocorticoids and other non-steroidal anti-inflammatory agents may aggravate gastro-intestinal side effects. Concurrent treatment with two or more non-steroidal anti-inflammatory (NSAIDs) agents may increase the occurrence of side u2013 effects. The bioavailability of AUSTELL DICLOFENAC is reduced by aspirin and that of aspirin by AUSTELL DICLOFENAC when the two agents are administered together.

Anticoagulants and anti-platelets

Increased risk of haemorrhage has been reported when AUSTELL DICLOFENAC has been used in combination with anticoagulant- and anti-platelet therapy. AUSTELL DICLOFENAC may enhance the effects of anti-coagulants such as warfarin.

Antidiabetics

Both hypoglycaemic and hyperglycaemic effects in the presence of AUSTELL DICLOFENAC, which necessitated changes in the dosage of hypoglycaemic agents have been reported.

Ciclosporin

Increased nephrotoxicity of ciclosporin may occur through effects of AUSTELL DICLOFENAC on renal prostaglandins.

Quinolone antibacterial

There have been isolated reports of convulsions, which may have been due to concomitant use of quinolones and non-steroidal anti-inflammatory drugs (NSAIDs) such as AUSTELL DICLOFENAC.

Selective serotonin reuptake inhibitors (SSRIs)

Concomitant use of NSAIDS and selective serotonin reuptake inhibitors (SSRIs) may increase the risk of gastro-intestinal bleeding (see section 4.4)

Pregnancy

The use of NSAIDS, such as AUSTELL DICLOFENAC used at 20 weeks gestation or later may cause serious kidney problems in an unborn baby. After around 20 weeks of pregnancy, the unborn babiesu2019 kidneys produce most of the amniotic fluid. Amniotic fluid provides a protective cushion and helps the unborn babiesu2019 lungs, digestive system, and muscles develop. Foetal renal dysfunction can lead to oligohydramnios due to the low levels of amniotic fluid. Complications of prolonged oligohydramnios may include limb contractures and delayed lung maturation (see section 4.2 and 4.4).

Use during the third trimester of pregnancy is contraindicated. The use of AUSTELL DICLOFENAC during the third trimester of pregnancy may result in closure of the foetal ductus arteriosus in utero, and possible persistent pulmonary hypertension of the newborn.

Breastfeeding

Diclofenac passes into breast milk in small amounts. Therefore, AUSTELL DICLOFENAC should not be administered during breastfeeding in order to avoid undesirable effects in the infant.

Fertility

The use of diclofenac may impair female fertility and is not recommended in woman attempting to conceive. In woman who have difficulties conceiving or who are undergoing investigation of infertility.

Occasionally people have reported that diclofenac sodium injections have made them feel dizzy, tired or sleepy. Problems with eyesight have also been reported. If you are affected in this way, you should not drive or operate machinery.

MedDRA System Organ Class Frequency Frequent Less Frequent Not known Infections and infestations Aseptic meningitis Injection site necrosis Blood and lymphatic system disorders Anaemia, thrombocytopenia, neutropenia, eosinophilia and agranulocytosis Immune system disorders Fever, angioedema, oedema, bronchospasm and rashes Hypersensitivity, anaphylactic and anaphylactoid reactions (including hypotension and shock) Angioneurotic oedema (including face oedema) Psychiatric disorders Disorientation, depression, insomnia, nightmare, irritability, psychotic disorder Nervous system disorders Headache, vertigo, dizziness, nervousness, tinnitus Depression, drowsiness and insomnia, paraesthesia, memory impairment, convulsion, anxiety, tremor, aseptic meningitis, taste disturbances, Confusion, hallucinations, disturbances of sensation, malaise cerebrovascular accident Eye disorders Visual disturbances, vision blurred, diplopia Optic neuritis Ear and labyrinth disorders Vertigo Hearing impaired Cardiac disorders Palpitations, chest pain, hypertension, and congestive cardiac failure Kounis syndrome Vascular disorders Hypertension, hypotension, vasculitis Respiratory, thoracic and mediastinal disorders Alveolitis, pulmonary eosinophilia, asthma (including dyspnoea), pneumonitis Gastrointestinal disorders Gastrointestinal discomfort, nausea, diarrhoea, vomiting, flatulence, dyspepsia, abdominal pain, anorexia Peptic ulceration, gastrointestinal bleeding and perforation, constipation, melaena, haematemesis, ulcerative stomatitis, gastritis, exacerbation of colitis and Crohnu2019s disease. Ischaemic colitis Hepatobiliary disorders Transaminases increased Hepatotoxicity, pancreatitis, hepatitis, jaundice, liver disorder, fulminant hepatitis, hepatic necrosis, hepatic failure Skin and subcutaneous tissue disorders Rash Bullous reactions, including Stevens-Johnson syndrome, toxic epidermal necrolyis and photosensitivity, urticaria, eczema, erythema, erythema multiforme, dermatitis exfoliative, loss of hair, purpura, allergic purpura, pruritus a) Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome Renal and urinary disorders Renal failure, nephropathy, haematuria, proteinuria, nephrotic syndrome, interstitial nephritis, renal papillary necrosis Reproductive system and breast disorders Impotence General disorders and administration site conditions Pain and tissue damage at the site of injection, oedema a) Drug Reaction with Eosinophillia and Systemic Symptoms (DRESS) (see section 4.4)

General symptoms of nausea, vomiting, headache, drowsiness, blurred vision and dizziness have been reported. There have been isolated case reports of more serious toxicity, including seizures, hypotension, apnoea, coma, and renal failure, although usually after ingestion of substantial quantities. Treatment is entirely supportive. Forced diuresis, haemodialysis, or haemoperfusion are unlikely to be of any benefit, although haemodialysis may be required if oliguric renal failure develops. There is no specific antidote.