(and dosage form):
Each capsule contains 25 mg Indomethacin.
A.3.1 Antirheumatics (Anti-inflammatory agents)
Indomethacin has anti-inflammatory and analgesic-antipyretic properties.
The analgesic properties of indomethacin are distinct from its anti-inflammatory effects. There is evidence for both a central and a peripheral effect.
Indomethacin inhibits prostaglandin synthesis and motility of polymorphonuclear leucocytes.
Pharmacokinetics and Metabolism:
Indomethacin is rapidly and almost completely absorbed from the gastro-intestinal tract. Peak plasma concentrations is attained within 2 hours in fasting subjects but may be somewhat delayed when taken after meals. Indomethacin is 90% bound to plasma proteins and also extensively bound to tissues.
The concentration of indomethacin in the cerebrospinal fluid is low.
Indomethacin is largely converted to inactive metabolites. About half of a single oral 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.
Entero-hepatic cycling of the conjugates takes place. 10 - 20% of the indomethacin is excreted unchanged in the urine, in part by tubular secretion. The plasma half-life is extremely variable and ranges between 2 and 11 hours.
Indomethacin is indicated for the treatment of ankylosing spondylitis, osteoarthritis, rheumatoid arthritis, acute gout and acute musculoskeletal disorders. Pain associated with dysmenorrhoea.
Sensitivity to indomethacin. Indomethacin should be administered with caution to patients with impaired renal function, epilepsy, parkinsonism or psychiatric disorders. It should not be given to patients with peptic ulcer or a history of gastro-intestinal lesions or to those who are sensitive to aspirin. Pregnancy and lactation.
Serious interactions have been reported after the use of high dose methotrexate with indomethacin. The combined use of indomethacin with diflunisal has been associated with fatal gastro-intestinal haemorrhage. Do not use indomethacin and diflunisal concomitantly.
DOSAGE AND DIRECTIONS FOR USE:
The usual initial dose in rheumatic disorders is 1 capsule (25 mg) two or three times daily with food or immediately after meals, (to lessen gastric distress) increased, if required, by 1 or 2 capsules (25 mg - 50 mg) daily at weekly intervals to 6 to 8 capsules (150 mg - 200 mg) daily. To alleviate night pain and morning stiffness, 4 capsules (100 mg) may be administered on retiring. In acute arthritis a dose of 2 capsules (50 mg) three times a day is suggested and in dysmenorrhoea up to 3 capsules (75 mg) daily.
SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
The commonest side-effects occurring with indomethacin are gastro-intestinal complaints and complications consisting in anorexia, nausea, and abdominal pain. Gastro-intestinal ulceration and bleeding may occur.
The most frequent central nervous system effect in chronic use is severe frontal headache. Dizziness, vertigo, light-headedness, and mental confusion are also frequent. Severe depression, psychosis, hallucinations, and suicide have occurred.
Prolonged therapy with indomethacin requires regular ophthalmological examinations.
Haematopoietic reactions include neutropenia, thrombocytopenia and aplastic anaemia. Deaths in children have occurred from what was probably overwhelming sepsis due to activation of latent infections.
Hypersensitivity reactions are manifested as rashes, itching, urticaria, and more seriously, acute attacks of asthma.
Other side-effects include drowsiness, tinnitus, insomnia, syncope, convulsions, coma, peripheral neuropathy, oedema and weight gain, hypertension, haematuria, skin rashes, pruritis, stomatitis and alopecia. Leucopenia, purpura, haemolytic anaemia, agranulocytosis, epistaxis, hyperglycaemia, hyperkalaemia, and vaginal bleeding have been reported.
There have also been reports of hepatitis and jaundice or renal failure.
In view of the product's inherent potential to cause fluid retention, heart failure may be precipitated in some compromised patients.
The total plasma concentration of indomethacin in addition to its inactive metabolites is increased by concurrent administration of probenecid. However, it has not been determined whether the concentration of free indomethacin in plasma is altered or whether the dosage of indomethacin must be adjusted when the two agents are administered together. Indomethacin does not interfere with the uricosuric effect of probenecid.
KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF IT'S TREATMENT:
Gastro-intestinal complaints and complications occur with overdosage presenting as anorexia, nausea, abdominal pain, and peptic ulcers sometimes with perforations and haemorrhage. Acute pancreatitis has been reported. The most frequent central nervous system effect is severe frontal headache. Treatment is symptomatic and supportive.
A yellow capsule containing a white powder.
Containers containing 100, 500 or 5000 capsules.
Store below 25°C. Protect from light and moisture.
KEEP OUT OF REACH OF CHILDREN.
NAME AND BUSINESS ADDRESS OF THE APPLICANT:
XIXIA Pharmaceuticals (Pty) Ltd.
15 Thora Crescent
Wynberg Ext. 3
P.O. Box 2080, Gallo Manor, 2052
DATE OF PUBLICATION OF THIS PACKAGE INSERT:
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