INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION
APO-DICLOFENAC 25 mg Tablets
APO-DICLOFENAC 100 mg Tablets

SCHEDULING STATUS:
S3

PROPRIETARY NAME
(and dosage form):

APO-DICLOFENAC 25 mg Tablets
APO-DICLOFENAC 100 mg Tablets

COMPOSITION:
Apo-Diclofenac 25 mg Tablets: Diclofenac sodium 25 mg/enteric-coated tablet.
Apo-Diclofenac 100 mg Tablets: Diclofenac sodium 100 mg/tablet.

PHARMACOLOGICAL CLASSIFICATION:
A 3.1 Antirheumatics (Anti-inflammatory agents).

PHARMACOLOGICAL ACTION:
Diclofenac sodium is a non-steroidal agent with anti-inflammatory, analgesic, antirheumatic and antipyretic properties.
Peak plasma concentrations of diclofenac 25 mg are reached within 1-4 hours and the agent is subject to first-pass metabolism. Excretion of the metabolites is mainly via the urine.
Diclofenac is 99.7% protein bound and has a mean terminal elimination half-life of 1-2 hours.

INDICATIONS:
Apo-Diclofenac (diclofenac sodium) is indicated for the symptomatic treatment of:

-	Rheumatoid arthritis and osteoarthrosis. It is also used to treat ankylosing spondylitis and spondyarthritis.
-	Post-operative and post-traumatic pain associated with inflammation and swelling.
-	Pain associated with dental surgery.
-	Treatment of the symptoms of primary dysmenorrhoea.

CONTRA-INDICATIONS:
Apo-Diclofenac (diclofenac sodium) is absolutely contra-indicated in patients with active, or recent history of peptic ulcer.
Diclofenac sodium is contra-indicated in patients with known or suspected hypersensitivity to diclofenac or any other non-steroidal anti-inflammatory agent.
Diclofenac is also contra-indicated in asthmatic patients in whom aspirin and other prostaglandin synthetase inhibitors have induced attacks of asthma, acute rhinitis or urticaria.
Diclofenac should not be administered during pregnancy and lactation or to patients with porphyria.

WARNINGS:
Apo-Diclofenac (diclofenac sodium) should be given under close medical supervision to patients prone to gastro-intestinal tract irritation particularly, those with a history of peptic ulcer, diverticulosis or other inflammatory disease of the gastrointestinal tract (such as ulcerative colitis or Crohn’s disease). Medical super-vision is also required for patients with pre-existing dyshaemopoiesis or disorders of blood coagulation.
Diclofenac should be used with caution in patients with hepatic or renal insufficiency. Serious interactions have been reported with the concomitant use of diclofenac and methotrexate.

DOSAGE AND DIRECTIONS FOR USE:
The maximum recommended daily dose for diclofenac sodium in any dosage form is 150 mg.
Apo-Diclofenac should be taken with food and the tablets should be swallowed whole.
Apo-Diclofenac 25 mg Tablets (enteric-coated)
The usual initial daily dose is 100 to 150 mg; in mild cases, Apo-Diclofenac treatment should be initiated with 75 mg to 100 mg per day. In general the daily dose should be divided into two or three fractional doses.
For the treatment of primary dysmenorrhoea, the dosage should be adapted to meet individual requirements. The daily dosage should be in the range of 50 to 150 mg.
Treatment should begin at the onset of symptoms and continue for a few days.
Apo-Diclofenac 100 mg Tablets
One tablet to be taken daily. If the symptoms most commonly occur at night or in the morning, the Apo-Diclofenac should be taken at night.
Apo-Diclofenac is not recommended for use in children.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
SIDE-EFFECTS:
Gastrointestinal System:

-	Epigastric pain, abdominal cramps and discomfort, dyspepsia, nausea, anorexia, diarrhoea, vomiting, flatulence, constipation or eructation and local irritation.
-	Gastric and duodenal ulcerations and bleeding.
-	Peptic ulcer with or without perforation, bloody diarrhoea, melaena, haematemesis.
-	Lower gut disorders (e.g. non-specific haemorrhagic colitis and exacerbation of ulcerative colitis).
-	Aphthous stomatitis, glossitis and oesophageal lesions.

Allergic:

-	Hypersensitivity reactions (eg: bronchospasm, anaphylactic/anaphylactoid systemic reactions including hypotension).
-	Fever and rashes
-	Hepatotoxicity
-	Aseptic meningitis

Central Nervous Systems:

-	Dizziness
-	Headache
-	Malaise, insomnia, drowsiness, impaired concentration, impaired vision, tiredness
-	Irritability, sweating
-	Vertigo, nervousness, disturbances of sensation, convulsions, paresthesia, impaired hearing, tinnitus, memory disturbance, disorientation, depression, anxiety, nightmares, tremor, psychotic reactions, taste alteration disorders.

Dermatologic System:

-	Rash and skin reactions
-	Pruritus
-	Skin eruption, eczema, urticaria, erythema
-	Photosensitivity reactions; loss of hair, erythema multiforme and variants (Stevens-Johnson Syndrome, Lyell Syndrome), erythroderma, purpura including allergic purpura.

Cardiovascular System:

-	Palpitation
-	Chest pain
-	Hypertension

Opthalmological:

-	Disturbances of vision (blurred vision, diplopia)
-	Changes in colour perception
-	Toxic amblyopia

Haematologic System:

-	Anaemia secondary to gastrointestinal bleeding
-	Leukopenia, thrombocytopenia, aplastic anaemia, agranulocytosis, haemolytic anaemia, neutropenia, eosinophilia

Oedema and Water Retention:

-	Peripheral oedema

Hepatic:

-	Elevation of serum aminotransferase enzymes (SGOT, SGPT)
-	Liver function disorders including hepatitis with or without jaundice.
-	Fulminant hepatitis

Respiratory System:

-	Asthma in patients sensitive to Acetylsalicylic Acid

Renal:

-	Acute renal failure
-	Urinary abnormalities indicating haematuria, proteinuria, interstitial nephritis, nephrotic syndrome and papillary necrosis
-	Cystitis

Other:

-	Impotence
-	Pancreatitis

PRECAUTIONS:
Gastro-intestinal bleeding or perforation may present at any time during diclofenac treatment.
This can present with or without warning symptoms or a previous history.
Elderly patients receiving diclofenac should be closely monitored, and the dosage reduced if necessary. The lowest effective dose should be used in the elderly, frail and low body mass patients.
Should gastro-intestinal bleeding or peptic ulceration occur during Apo-Diclofenac treatment, the treatment must be withdrawn.
Due to the fluid retention caused by diclofenac, heart failure may be induced in susceptible patients.
Due to the fact that prostaglandins are important where renal blood flow is concerned, careful monitoring is required for the following patients:

-	Patients with impaired hepatic, cardiac or renal function.
-	Elderly patients being treated with diuretics.
-	Patients with extracellular volume depletion.
-	Patients with cirrhosis

Elevations of one or more of the liver enzymes may occur with diclofenac treatment. Should these abnormal liver functions tests persist or if clinical signs of liver disease develop, Apo-Diclofenac should be discontinued.
Hepatitis may occur.
Allergic reactions including anaphylaxis can occur, even without prior exposure.
Patients who experience central nervous system reactions should refrain from driving and operating hazardous machinery.
Patients receiving long term diclofenac therapy should undergo periodic blood counts.
Patients with collagen disease are at increased risk of developing aseptic meningitis.
Diclofenac therapy should be discontinued in patients who experience blurred vision or changes in colour vision.
Interactions:
Diclofenac may raise plasma concentrations of digoxin or lithium when used concomitantly.
Concomitant administration with glucocorticoids or other non-steroidal anti-inflammatory agents may exacerbate gastro-intestinal side-effects.
Bioavailability of diclofenac is reduced by acetylsalicylic acid when the two medicines are administered concomitantly.
When diclofenac is used together with anticoagulent therapy, the patient must be closely monitored due to the increased risk of haemorrhage.
Use of diclofenac in diabetic patients requires close monitoring of blood sugar and possible alterations in the dosage of hypoglycaemic agents.
The nephrotoxicity of cyclosporin may be increased when used together with Apo-Diclofenac.
Diclofenac may cause increased levels of methotrexate.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
See Side-Effects and Special Precautions.
Treatment is symptomatic and supportive.
There is no specific antidote for diclofenac.

IDENTIFICATION:
Apo-Diclofenac (diclofenac sodium) 25 mg Tablets: round, mustard yellow, biconvex, coated tablets, engraved '25' on one side.
Apo-Diclofenac (diclofenac sodium) 100 mg Tablets: round, pink, biconvex tablet, bevel edged, one side engraved 'APO' over '100', other side plain.

PRESENTATION:
Apo-Diclofenac 25 mg tablets are packaged in white, plastic bottles of 100 and 500.
Apo-Diclofenac 100 mg tablets are packaged in white, plastic bottles of 30, 100 and 250.

STORAGE INSTRUCTIONS:
Store below 25°C. Protect from light and moisture.
KEEP OUT OF REACH OF CHILDREN

REGISTRATION NUMBERS:
Apo-Diclofenac 25 mg - 30/3.1/0166
Apo-Diclofenac 100 mg - 30/3.1/0160

NAME AND BUSINESS ADDRESS OF THE APPLICANT:
APOTEX S.A.
PHARMACEUTICAL INNOVATION
Apotex S.A. (Pty) Ltd.
Cnr Fleming & Watt Streets
Meadowdale Ext. 1

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
March 1996
                        P300166/300160/3
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