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Logo ARTHREXIN® SUPPOSITORIES

SCHEDULING STATUS:
S3

PROPRIETARY NAME
(and dosage form):

ARTHREXIN® SUPPOSITORIES

COMPOSITION:
Each suppository contains 100 mg
Indomethacin.

PHARMACOLOGICAL CLASSIFICATION:
A 3.1 Antirheumatics (anti-inflammatory agents)

PHARMACOLOGICAL ACTION:
Indomethacin has prominent anti-inflammatory and anti-pyretic properties in experimental animals similar to those of the salicylates. Comparable effects have been demonstrated in man. The anti-inflammatory effects of indomethacin are evident in patients with rheumatoid and other types of arthritis and in acute gout. Although indomethacin is more potent than aspirin, the anti-inflammatory effects of tolerated doses of indomethacin in rheumatoid arthritis are not superior to those of salicylate. Whether indomethacin has analgesic properties distinct from its anti-inflammatory effects remains uncertain. However, in patients with acute post-operative and post-traumatic pain of mild to moderate intensity, single doses of indomethacin provide relief approximately equivalent to that of 600 mg of aspirin. The antipyretic effect of indomethacin has also been readily demonstrated in patients with fever. Single doses of indomethacin are usually adequately tolerated; however, because of its potential toxicity, indomethacin is not recommended as a general analgesic-antipyretic.
Like the salicylates and related anti-inflammatory agents indomethacin inhibits the biosynthesis of prostaglandins; this action may be the basis of its anti-inflammatory and antipyretic properties and certain of its other effects. Like colchicine, it inhibits motility of polymorphonuclear leucocytes; like salicylate, it uncouples oxidative phosphorylation in cartilaginous and hepatic mitochondria.
Indomethacin is rapidly and almost completely absorbed. Peak plasma concentration is attained within 3 hours in the fasting subject but may be somewhat delayed when the medicine is taken after meals. Indomethacin is 90% bound to plasma proteins and also extensively bound in tissues. The concentration of the medicine in the central spinal fluid is low.
Contrary to initial impression indomethacin is largely converted to inactive metabolites. About half a single dose is 0-demethylated and about 10% is conjugated with glucuronic acid by the hepatic microsomal enzymes. A portion is also N-deacylated by a non-microsomal system. Some of these metabolites are detectable in plasma, and free and conjugated metabolites are eliminated in the urine, bile and faeces. Enterohepatic cycling of the conjugates occurs. Ten to 20% of the medicine is excreted unchanged in the urine, in part by tubular secretion. The plasma halflife of the unchanged medicine is about 2 hours.
The reported antagonism between indomethacin and aspirin in some laboratory tests for anti-inflammatory activity has provoked speculation that similar antagonism might occur during therapy. In man, the slight reduction in the plasma concentration of indomethacin by aspirin does not appear to be of practical significance. Whether it reflects displacement of bound indomethacin from plasma protein has not been determined. The total plasma concentration of indomethacin plus its inactive metabolites is increased by concurrent administration of probenecid. However, it has not been determined whether the concentration of unchanged indomethacin not bound to plasma protein is altered, or whether the dosage of indomethacin must be adjusted when the two drugs are employed together. Indomethacin does not interfere with the uricosuric effect of probenecid.

INDICATIONS:
To relieve the painful symptoms of ankylosing spondylitis and osteoarthritis, and to relieve the pain and swelling in gout, rheumatoid arthritis and acute musculoskeletal disorders. It has also been used to reduce symptoms in some febrile conditions. It has proved useful as an antipyretic in Hodgkin's disease when the fever has been refractory to other therapy.

CONTRA-INDICATIONS:
Indomethacin should be administered with caution to patients with impaired hepatic or renal function, psychiatric disorders, epilepsy and parkinsonism. It should not be given to patients with a history of peptic ulcer. It is suggested that it should not be administered during pregnancy.
The suppositories are contra-indicated in patients with a recent history of proctitis; and must be used with caution in patients with a recent history of rectal bleeding.

DOSAGE AND DIRECTIONS FOR USE:
Cut one suppository off, separate the plastic foil and pull to release suppository.
Immerse in water (room temperature) before inserting.
To provide relief during the night and to alleviate painful symptoms the following morning, 100 mg may be administered as a suppository on retiring.

[illustrated]

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Headache and dizziness occur frequently at the commencement of treatment and may disappear if the dose is reduced. Anorexia, nausea and vomiting, dyspepsia and diarrhoea may occur and are usually unrelated to the dosage. Peptic ulceration, possibly with gastro-intestinal haemorrhage may also occur and is not always preceded by dyspepsia. Other reported toxic effects include blood dyscrasias, haematuria, oedema and skin rashes.
Haemopoietic reactions consist of neutropenia, thrombocytopenia and rarely, aplastic anaemia. Deaths in children have occurred from what was probably overwhelming sepsis due to activation of latent infections. Severe depression, psychosis, hallucinations and suicide have been reported. Corneal opacities, visual-field changes and pallor of the optic disc have also occurred.
Indomethacin is said not to modify the effects of the oral anticoagulant agents. However concurrent administration could be hazardous because of the increased risk of gastro-intestinal bleeding. Prolonged therapy with Arthrexin will require ophthalmological examination. Few patients tolerate more than 100 mg per day without severe side effects. Because of the severity and high incidence of side-effects associated with chronic administration, the use of indomethacin as a general analgesic-antipyretic is not recommended. Prolonged therapy will require ophthalmological examinations.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
Overdosage does not readily occur with the use of suppositories. Gastro-intestinal complaints occur with overdosage, causing nausea, pain and peptic ulcers, often with bleeding, and perforation. Acute pancreatitis has been reported. The most frequent CNS effect is severe frontal headache, occurring in 25 to 50% of patients who take the medicine chronically.

CONDITIONS OF REGISTRATION:
May be advertised to the profession only.

IDENTIFICATION:
A White to off-white torpedo-shaped suppository.

PRESENTATION:
Premoulded pack containing 10 suppositories.

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

REGISTRATION NUMBER:
K/3.1/222.

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

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
07/09/1988

G362B
KOHLER C&P P E

Current: September 2004
Source: Community Pharmacy

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