Oxytetracycline Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Oxytetracycline Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Oxytetracycline Dihydrate BP 250 mg
3 PHARMACEUTICAL FORM
Sugar-coated tablet
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Therapeutic Indications
1. In infections caused by the following micro- organisms:
Rickettsiae (Rocky Mountain spotted fever, typhus fever and the typhus group, Q fever, rickettsialpox and tick fevers).
Mycoplasma pneumoniae (PPLO, Eaton Agent).
Agents of psittacosis and ornithosis.
Agents of lymphogranuloma venereum and granuloma inguinale.
The spirochaetal agent of relapsing fever (Borrelia recurrentis).
The following Gram-negative micro-organisms:
Haemopbilus ducreyi (chancroid).
Pasteurella pestis and Pasteurella tularensis.
Bartonella bacilliformis.
Bacteroides species.
Vibrio comma and Vibrio fetus.
Brucella species (in conjunction with streptomycin).
Because many strains of the following groups of micro-organisms have been shown to be resistant to tetracyclines, culture and susceptibility testing are recommended.
2. For treatment of infections caused by the following Gram negative microorganisms, when bacteriological testing indicates appropriate susceptibility to the drug:
Escherichia coli.
Enterobacter aerogenes.
Shigella species.
Mima species and Herellea species.
Haemophilus influenzae (respiratory infections).
Klebsiella species (respiratory and urinary infections).
3. For treatment of infections caused by the following Gram-positive microorganisms when bacteriological testing indicates appropriate susceptibility to the drug:
Streptococcus species.
Diplococcus aureus (skin and soft tissue infections).
When penicillin is contra-indicated tetracyclines are alternative drugs in the treatment of infections due to:
Neisseria gonorrhoea.
Treponema pallidum and Treponema pertenue (syphilis and yaws).
Listeria monocytogenes.
Clostridium species.
Bacillus anthracis.
Fusiformis fusiformis (Vincent’s infection).
Actinomyces species.
4. In acute intestinal amoebiasis. May be a useful adjunct to amoebicides.
5. In severe acne, may be useful adjunctive therapy.
6. Indicated in the treatment of trachoma, although the infectious agent is not always eliminated, as judged by immunofluorescence.
Inclusion conjunctivitis may be treated with oral tetracyclines or with a combination of oral and topical agents.
4.2 Posology and method of administration Adults:
1 g daily in divided doses given as 250 mg four times daily. Higher doses such as 500 mg four times daily may be required for severe infections or for those infections which do not respond to the smaller dose.
Brucellosis, 500 mg four times daily accompanied by streptomycin.
Gonococcal infections: Male and female, 1.5 g initially followed by 0.5 g four times daily for a total of 9 g.
Syphilis, a total of 30-40 g in equally divided doses over a period of ten to fifteen days should be given.
Children:
Not recommended for children under 12 years of age.
Usual daily dose for children of 12 years and above: 25-50 mg/kg (10-20 mg/lb) of bodyweight divided in four equal doses.
Elderly:
May be given at the usual adult dosage. The possibility of sub-clinical renal insufficiency should be kept in mind, as it may lead to drug accumulation.
Therapy should be continued for at least 24-48 hours after symptoms and fever have subsided.
In the treatment of streptococcal infections, a therapeutic dose should be administered for at least ten days.
Oral forms of oxytetracycline should be given one hour before or two hours after meals.
In patients with renal impairment the total dosage should be decreased either by reduction of the recommended individual dosage or by extending the time interval between doses or a combination of both.
4.3 Contraindications
Oxytetracycline is contraindicated in patients who have shown hypersensitivity to any of the tetracyclines, in patients with systemic lupus erythematous and in children under 12 years of age.
Oxytetracycline should not be administered during pregnancy as there is evidence of embryo-toxicity with predominant effects on teeth and skeletal development. Tetracyclines are excreted into breast milk and are therefore contraindicated in nursing mothers.
Oxytetracycline should not be administered in cases of renal impairment due to the risk of excessive drug accumulation and liver toxicity.
4.4 Special warnings and precautions for use
Use during tooth development (last half of pregnancy, infancy and childhood to the age of 12 years) may cause permanent discolouration of the teeth (yellow-green-brown). Enamel hypoplasia has also been reported. The drug should therefore not be used in this age group.
Conditions of renal impairment: Treatment with usual doses may give rise to excessive systemic accumulation of the drug with possible liver toxicity. It is therefore necessary under these circumstances to treat with lower than usual total doses and particularly when therapy is prolonged, serum level determination may be advisable. In patients with significantly impaired renal function, raised serum levels of the drug may lead to acidosis, hyperphosphataemia and azotaemia.
Oxytetracycline should be administered with caution to patients with hepatic dysfunction or in conjunction with other potentially hepatotoxic drugs.
Oxytetracycline may cause overgrowth of non-susceptible organisms. If such superinfection occurs, the drug should be discontinued and appropriate therapy introduced. Oxytetracycline depresses prothrombin activity and consequently patients who are on anti-coagulant therapy may require a lowering of their anticoagulant dosage.
It is advisable in long-term therapy to undertake periodic laboratory evaluation of the haematopoietic, renal and hepatic systems.
Photosensitivity has been observed in some patients taking oxytetracycline as evidenced by an exaggerated sunburn reaction. Patients should avoid direct exposure to natural or artificial sunlight and discontinue therapy at the first sign of skin discomfort.
Oxytetracycline is unsafe for use in acute porphyrias. It may exacerbate symptoms of systemic lupus erythematous and may cause weak neuromuscular blockade in Myasthenia Gravis.
4.5 Interaction with other medicinal products and other forms of interaction
Tetracyclines bind to di-/tri-valent cations. Absorption from the gastrointestinal tract is impaired by the concomitant administration of iron, calcium, aluminium, magnesium, bismuth and zinc salts. Possible interactions may therefore occur with the specified salts, antacids, bismuth containing ulcer-healing drugs and quinopril which contains magnesium carbonate. Dosages should be maximally separated.
Food and some dairy products also interfere with absorption. It is advisable to avoid giving tetracyclines in conjunction with penicillin. The concomiant use of tetracyclines may reduce the efficacy of oral contraceptives.
An increase in anticoagulant effect may occur with tetracyclines. Diuretics may aggravate nephrotoxicity by volume depletion.
Atovaquone plasma concentration is reduced by concomitant use of tetracyclines.
Concommitant use with retinoids should be avoided as there may be an increased risk of benign intercranial hypertension.
4.6 Pregnancy and lactation
Animal studies show that tetracyclines have crossed the placenta and are found in foetal tissues where they can have toxic effects on the developing foetus, there is evidence of embryo toxicity in animals treated early in pregnancy. Tetracyclines are present in the milk of lactating women where they form a stable calcium complex in all bone forming tissue.
4.7 Effects on ability to drive and use machines
Does not affect ability to drive and use machines.
4.8 Undesirable effects
Side effects:
Gastro-intestinal: Anorexia, nausea, vomiting, diarrhoea, rarely dysphagia and inflammatory lesions (with monilial overgrowth) in the anogenital region. Rare instances of oesophagitis and oesophageal ulcerations have been reported in patients receiving capsule and tablet forms, usually when taken before bed or with inadequate fluids. A few cases of pancreatitis have been reported. As with all antibiotics overgrowth of non-suceptible organisms may cause candidiasis, pseudomembranous colitis due to Clostridium difficile overgrowth, glossitis, stomatitis, vaginitis or staphylococcal enterocolitis.
Skin: Maculopapular and erythematous rashes, pruritis and bullous dermatoses. Exfoliative dermatitis has been reported but is rare. Photosensitivity.
Hypersensitivity reactions: Urticaria, angioneurotic oedema, anaphylaxis, anaphylactoid purpura, pericarditis and exacerbation of systemic lupus erythematosus.
Blood: Haemolytic anaemia, thrombocytopenia, neutropenia and eosinophilia have been reported.
Other: Bulging fontanelles in infants and benign intracranial hypertension in juveniles and adults have been reported. Symptoms are headache and visual disturbances including blurring of vision, scotomata and diploplia. These conditions disappear rapidly when the drug is discontinued although permanent visual loss has been reported.
When given over prolonged periods, tetracyclines may produce brown-black microscopic discoloration of thyroid glands. No abnormalities of thyroid function are known to occur.
Transient increases in liver function tests, hepatitis, jaundice and hepatic failure have been reported on rare occasions.
Teeth discolouration is more common during long-term use of the drug but has been observed following repeated short-term doses.
4.9 Overdose
Although overdosage with antibiotics is rare, then if it should occur gastric lavage plus appropriate supportive therapy is indicated.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Oxytetracycline is primarily a bacteriostatic antibiotic and has a similar spectrum of activity to other tetracyclines.
Oxytetracycline is a broad spectrum antibiotic to sensitive organisms.
5.2 Pharmacokinetic properties
Oxytetracycline is absorbed irregularly to the extent of about 60% of an oral dose, absorption occurring in the stomach and upper small intestine.
Peak plasma concentrations achieved 2-4 hours after an oral dose.
The mean plasma half-life is 9.2 hours. The plasma/protein bind is 27-35%. The drug is eliminated largely unchanged mostly in the urine, with some in the faeces. A small amount is metabolised in the liver.
5.3 Preclinical safety data
Not applicable.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Maize starch
Pregelatinised maize starch
Povidone K25
Industrial methylated spirits
Purified water
Sodium starch glycollate
Sodium lauryl sulphate
Magnesium stearate
Sucrose
Talc
Yellow 1409 (E102)
Dispersed Yellow 1564 (E102)
6.2 Incompatibilities
Incompatibility has been reported with alkali, aminophyline, amphotericin, ampicillin sodium, soluble barbiturate, benzyl penicillin, carbenicillin sodium, cefaprin sodium, cephaloridine, cephalothin sodium, cephazolin sodium, doxicillin sodium, erythromycin salts, iron dextran injection, methicillin sodium, novobiocin sodium, oxacillin sodium, sodium bicarbonate, sulphadiazine sodium, sulphafurazole, diethanolamine,. Incompatibility, although less consistently, has also been reported with calcium chloride, calcium gluconate, chloramphenicol, sodium succinate, lactated Ringer’s injection, protein hydrolysate, sodium lactate and amikacin sulphate (depending on dilution of the latter).
6.3 Shelf life
24 Months.
6.4 Special precautions for storage
Store below 25 °C in a dry place in well closed containers.
6.5 Nature and contents of container
High density polystyrene or polypropylene containers. Pack size: 500 tablets
6.6 Special precautions for disposal
Not applicable.
7 MARKETING AUTHORISATION HOLDER
Chelonia Healthcare Limited
Boumpoulinas 11, 3 rd Floor
NICOSIA
CYPRUS
PC. 1060
CYPRUS
MARKETING AUTHORISATION NUMBER(S)
PL 33414/0075
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DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
1972 19/11/1990
DATE OF REVISION OF THE TEXT
May 2001
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