FLEXAGEN-25 TABLETS; FLEXAGEN-50 TABLETS; FLEXAGEN-75 INJECTION

INDICATIONS CONTRA-INDICATIONS DOSAGE SIDE-EFFECTS PREGNANCY OVERDOSE IDENTIFICATION PATIENT INFORMATION

FLEXAGEN-25 TABLETS
FLEXAGEN-50 TABLETS
FLEXAGEN-75 INJECTION

SCHEDULING STATUS:
S3
S2 (See Indications below)

PROPRIETARY NAME
(and dosage form):

FLEXAGEN-25 TABLETS
FLEXAGEN-50 TABLETS
FLEXAGEN-75 INJECTION

COMPOSITION:
Each coated tablet (which is also enteric coated) contains either 25 mg or 50 mg diclofenac sodium.
Each 3 mL ampoule contains 75 mg diclofenac sodium, 0,3% m/v sodium metabisulphite and 4% v/v benzyl alcohol as preservative.

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

PHARMACOLOGICAL ACTION:
Diclofenac sodium is a non-steroidal compound with analgesic, anti-inflammatory, antirheumatic and antipyretic properties. A single 50 mg dose of enteric coated tablets results in maximum plasma concentrations of about 1500 ng/mL at 1,5 to 2 hours after ingestion.
Diclofenac sodium is eliminated principally by metabolism and subsequent urinary and biliary excretion of glucuronide and sulphate conjugates of the metabolites. The principal metabolite in man is the 4-hydroxy derivative of diclofenac sodium. The amount excreted in urine accounts for 20 to 30 % of the dose and that in bile for 10 to 20%. The mean terminal elimination half-life is 1,2 to 1,8 hours.

INDICATIONS:

Tablets S3:	Rheumatoid arthritis, osteo-arthritis and ankylosing spondylitis.
	Treatment of post traumatic pain and inflammation. Symptomatic treatment of primary dysmenorrhoea.
Injection S3:	For use as initial therapy for inflammatory and degenerative rheumatic diseases. Painful conditions due to inflammation of non-rheumatic origin and acute attacks of gout.
All dosage forms S2:	Emergency treatment of acute gout attacks. Treatment of post-traumatic conditions such as pain, swelling and inflammation for a maximum period of 5 days.

CONTRA-INDICATIONS:
Patients with porphyria. Children under the age of two years. Patients with a history of, or active gastro-intestinal bleeding or peptic ulceration. Severe hepatic or renal impairment. Contra-indicated in aspirin sensitive patients, and in patients sensitive to any of the ingredients in these products.
Safety during pregnancy and lactation has not yet been established.

WARNING:
Serious interactions have been reported after the use of high dose methotrexate with diclofenac.

DOSAGE AND DIRECTIONS FOR USE:
Flexagen-25 and Flexagen-50 Tablets:
In adults, the dosage is 25 to 50 mg three times daily depending on the severity of the condition. The maintenance dose should be adjusted to the minimum that will provide continuous therapeutic control. The tablets should be swallowed whole, with or after a meal. The dosage in children is 2 mg per kilogram body mass per day in three divided doses.

Flexagen-75 Injection:
75 mg by deep intragluteal injection once daily, or two times daily, in severe or hospitalized cases. Each injection must be given at a different site. Not to be given by intravenous injection. Each injection should be separated by an interval of a few hours. Parenteral administration should not be given for more than a few days, if necessary the treatment can be continued by oral therapy.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Gastro-intestinal disorders including epigastric pain, eructation, nausea and vomiting may occur. Peptic ulceration and gastro-intestinal bleeding have been reported. Other side-effects include vertigo, headache, skin rashes, pruritus, tinnitus, depression, drowsiness, nervousness, insomnia, irritability, agitation, minor hearing disorders, oedema, palpitations, blurred vision and other ocular reactions.

Hypersentivity reactions may occur and include fever and rashes. Hepatotoxicity and aseptic meningitis which occur less frequently may also be hypersensitivity reactions.

Diclofenac may cause cystitis and haematuria, as well as acute renal failure, interstitial nephritis and nephrotic syndrome.

Other adverse effects include anaemia, thrombocytopenia, neutropenia, eosinophilia, agranulocytosis and abnormalities in liver function tests.

Patients with congestive heart failure, cirrhosis, diuretic-induced volume depletion or renal insufficiency are at greater risk of developing renal dysfunction due to non-steroidal anti-inflammatory medicine-induced inhibition of renal prostaglandin synthesis.

It is advisable to perform blood counts in patients undergoing prolonged treatment.

Flexagen should be given with care to patients with cardiovascular disease, bleeding disorders in those who are receiving coumarin anti-coagulants, and in patients with impaired hepatic or renal function.

Allergic reactions which include angio-oedema, bronchospasm, urticaria and anaphylactic reactions, have occurred. Because of the possibility of cross-sensitivity due to structural relationships which exist among nonsteroidal anti-inflammatory medicines, acute allergic reactions may be more likely to occur in patients who have exhibited allergic reactions to these compounds.

Plasma concentrations are significantly decreased by the concomitant administration of therapeutic doses of aspirin.

When given together with preparations containing lithium or digoxin, diclofenac sodium may raise their plasma concentrations. Concomitant administration of glucocorticoids or other non-steroidal anti-inflammatory agents may aggravate gastro-intestinal side-effects.

Concurrent administration with two or more non-steroidal anti-inflammatory agents may promote the occurrence of side-effects.

Should be used with caution in patients with asthma or bronchoconstriction.

Use with care in elderly patients.

Decreased platelet aggregation with increased bleeding time may occur.

May increase the half-life of probenecid.

Use with care together with other protein-bound medicines e.g. Tolbutamide, Coumarin and Hydantoin.

In view of the product's inherent potential to cause fluid retention, heart failure may be precipitated in some compromised patients.

KNOWN SYMPTOMS OT OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
See 'Side-effects and special precautions'. Treatment is symptomatic and supportive.

IDENTIFICATION:

25 mg Tablet	Yellowish-mustard, film-coated, shallow biconvex tablet (which is also enteric-coated).
50 mg Tablet	Light brown, film-coated, shallow biconvex tablet (which is also enteric coated).
75 mg/3 mL Injection	Clear colourless to slight straw-coloured solution in amber ampoules.

PRESENTATION:

25 mg Tablet	Securitainers of 30, 100 and 500 tablets.
50 mg Tablet	Securitainers of 21 and 500 tablets.
75 mg/3 mL Injection	Amber glass ampoules in packs of 5 and 50.

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

REGISTRATION NUMBERS:

25 mg tablet	27/3.1/0314
50 mg tablet	27/3.1/0315
75 mg/3 mL Ampoules	27/3.1/0293

NAME AND BUSINESS ADDRESS OF APPLICANT:
Lennon Limited
7 Fairclough Road
PORT ELIZABETH, 6001

DATE OF PUBLICATION OF THIS PACKAGE INSERT:

November 1993	12-026/7-95
	KOHLER C&P P E