COMPOSITION: TRITET is supplied in a 300 mg dosage form and is the first formulation containing three effective tetracycline antibiotics, each of which possesses a broad spectrum of activity and a low degree of toxicity. The three components are combined in a 1:1:0,6 ratio, as follows:
PHARMACOLOGICAL CLASSIFICATION: Category A, 20.1.1 Broad- and medium spectrum antibiotics.
PHARMACOLOGICAL ACTION: Tetracyclines are broad spectrum antibiotics they are bacteriostatic against a wide range of Gram-positive and Gram-negative organisms. Tetracyclines are particularly useful in infections caused by Haemophilus ducreyi, Brucella, Vibrio cholerae, Pseudomonas (Actinobacillus) mallei and pseudomallei, and Calymmatobacterium (Danovania) granulomatis. Tetracyclines also inhibit the growth of Yersinia (Pasteurella) pestro, Francisella (Past.), tularensis and Past. multocida. More variable success is achieved with infections due to Escherichia coli, Klebsiella, Enterobacter (Aerobacter), Bactericides, H. influenzae and indole-producing strains of Proteus. Tetracyclines are effective against certain rickettsiae and larger viruses responsible for Rocky Mountain spotted fever, Tickbite Fever, murine typhus, epidemic typhus, scrub typhus, rickettsial pox and Q fever. Tetracyclines are also effective in relapsing fever (Borrelia recurrentis) and are valuable secondary agents against the spirochetes Treponema pallidum, T. pertenue, and Leptospira interrogans. High concentrations inhibit the growth of the protozoan Entamoeba histolytica. Certain organisms known to have been sensitive may have lost their sensitivity to tetracyclines.
Many strains of staphylococci and enterococci and nearly all strains of Proteus vulgaris and Pseudomonas aeruginosa are relatively resistant. With the exception of Actinomyces spp., fungi and yeasts are resistant. Tetracyclines are adequately but incompletely absorbed from the intestinal tract. Effective blood levels are reached in about two to four hours after oral administration and are maintained with recommended dosages. Absorption is diminished by the presence of iron, aluminium, calcium and magnesium.
Tetracyclines are widely distributed into pleural and peritoneal fluid, saliva, semen and prostatic fluid, and under certain circumstances, into cerebrospinal fluid. Tetracyclines pass the placental barrier readily and are also present in the milk of lactating patients. They are concentrated by the liver and excreted, by way of the bile, into the intestine from which they are partially reabsorbed. Excretion in the urine also takes place. Based on the serum in vitro activity, the twice daily dosage of triple tetracycline is a means of obtaining therapeutic levels of tetracycline.
INDICATIONS: TRITET (demethylchlortetracycline - tetracycline - chlortetracycline) is indicated for the treatment of bacterial and Rickettsial diseases.
TRITET is also indicated for the treatment of infections produced by Mycoplasma and in disorders caused by Chlamydia. Given concomitantly with other drugs they are effective in some instances of intestinal amoebiasis.
TRITET is indicated for the treatment of various infectious diseases e.g. Rocky Mountain spotted fever, Tickbite Fever, murine typhus, recrudescent epidemic typhus, scrub typhus, Q fever, lymphogranuloma venereum, psittacosis, tularemia, brucellosis.
TRITET may be used in the treatment of gonorrhoea, syphilis and anthrax in cases where the patient is hypersensitive to penicillin.
CONTRA-INDICATIONS: Tetracycline is not recommended for use in cases of renal dysfunction or liver damage. It should be used during pregnancy and in children under the age of 12 years only under very exceptional circumstances.
WARNINGS: As preparations containing iron, aluminium, calcium or magnesium decrease the absorption of tetracycline, do not give to patients receiving antacid therapy, milk or calcium containing foods.
DOSAGE AND DIRECTIONS FOR USE: The usual daily dosage for adults is one 300 mg capsule every 12 hours. In the more severe infections, it may be necessary to increase the number of daily capsules to three or four, but continuation of high dosages beyond the first few days is thought to be unnecessary.
Therapy should be continued for one to three days after characteristic symptoms or fever have subsided.
Absorption of the tetracycline is impaired by the concomitant administration of milk products, calcium and magnesium salts and particularly antacids containing aluminium hydroxide or silicate. The preferred time of administration is one hour before or two hours after meals.
In the treatment of syphilis a dosage schedule of a total of 12 to 18 g given in equally divided doses over a period of 10 to 15 days is suggested. Close follow-up observation of the patient is recommended, including appropriate laboratory tests, since this product has not adequate evaluation in all stages of syphilis. Spinal fluid examination should be included as part of the follow-up.
SIDE-EFFECTS AND SPECIAL PRECAUTIONS: Side-effects include nausea, diarrhoea, and symptoms resulting from the overgrowth of non-susceptible organisms. Overgrowth of Candida albicans in the mouth causes soreness, redness, and thrush, which may extend into the trachea and bronchi; overgrowth of C. albicans in the bowel results in pruritis ani and there may be overgrowth of resistant coliform organisms, such as Pseudomonas spp. and Proteus spp., causing diarrhoea. The most serious supra-infection is by resistant staphylococci, causing a fulminating enteritis with dehydration and, occasionally death; this complication is rare, except after abdominal surgery, especially gastrectomy.
Therapeutic doses given to patients with renal disease increase the severity of azotaemia with increased excretion of nitrogen and losses of sodium and, in severe cases, symptoms suggestive of uraemia with development of anorexia, nausea, vomiting, and weakness, accompanied by acidosis and hyperphosphataemia.
Occasionally severe and sometimes fatal liver damage has occurred in pregnant women treated with a tetracycline for pyelonephritis, especially when large doses have been given intravenously. Tetracyclines are deposited in calcifying areas in bone and in teeth, causing permanent discolouration and malformation; when given in therapeutic doses to young infants or to women during the late stages of pregnancy tetracyclines interfere with the growth of bones and teeth in infants. Milk teeth are affected if given to children three months to six years, and permanent teeth if given to children up to 12 years. An increase in intracranial pressure, which may be associated with a bulging fontanelle in infants, has been reported in patients given tetracyclines.
Allergic reactions to tetracycline and its analogues have been reported on rare occasions; photosensitivity has occurred after large doses of demethylchlortetracycline, and less frequently after tetracycline and oxytetracycline.
A syndrome like the adult (acquired) type of Fanconi syndrome, with nausea, vomiting, proteinuria, glycosuria, acidosis, and amino-aciduria commencing within 2 or 3 days of starting treatment, has been attributed to the degradation products epianhydrotetracycline and anhydrotetracycline, developed on storage in the presence of heat and moisture.
KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT: In the event of sensitivity reactions, treatment should be withdrawn.
CONDITIONS OF REGISTRATION: May be advertised to the professions only.
IDENTIFICATION: TRITET is a caramel and flesh coloured capsule.
PRESENTATION: Securitainers of 10 and 100 capsules.
STORAGE INSTRUCTIONS: Store in a cool (below 25°C), dry place. Keep out of the reach of children.
REGISTRATION NUMBER: C/20.1.1/58
NAME AND BUSINESS ADDRESS OF APPLICANT: AKROMED PRODUCTS
Electron Avenue ISANDO 1600
Trademark and product,
under licence from
WYETH-AYERST LABORATORIES, U.S.A.
DATE OF PUBLICATION OF THIS PACKAGE INSERT: 20 May 1990