Oxytetracycline Tablets Bp 250mg
SUMMARY OF PRODUCT CHARACTERISTICS
1. NAME OF THE MEDICINAL PRODUCT
Oxytetracycline Tablets BP 250 mg
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 269.57 mg of oxytetracycline dihydrate equivalent to 250mg of oxytetracyline.
Excipients with known effect: Also contains sucrose, glucose and tartrazine aluminium lake (E102).
For the full list of excipients, see section 6.1.
3. PHARMACEUTICAL FORM
Tablet
A yellow sugar-coated tablet with a smooth polished surface 4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Oxytetracycline is a bacteriostatic broad-spectrum antibiotic, active against a wide variety of Gram-positive and Gram-negative organisms.
Infections caused by oxytetracycline-sensitive organisms include:
1) Respiratory tract infections: Pneumonia, whooping cough and other lower respiratory tract infections due to susceptible strains of Streptococcus pneumonia, Haemophilus influenza, Klebsiella pneumonia and other organisms. Mycoplasma pneumoniae pneumonia. Treatment of chronic bronchitis (including the prophylaxis of acute exacerbations).
2) Urinary tract infections: caused by susceptible strains of the Klebsiella species. Enterobacter species, Escherichia coli, Streptococcus faecalis and other organisms.
3) Sexually transmitted diseases: Infections due to Chlamydia trachomatis including uncomplicated urethral, endocervical or rectal infections. Nongonococcal urethritis caused by Ureaplasma urealyticum. Oxytetracycline is also indicated in chancroid, granuloma inguinale and lymphogranuloma venereum. Oxytetracycline is an alternative drug in the treatment of gonorrhoea and syphilis.
4) Skin Infections: Acne vulgaris when antibiotic therapy is considered necessary and severe rosacea.
5) Ophthalmic infections: Trachoma, although the infectious agent, as judged by immunofluorescence, is not always eliminated. Inclusion conjunctivitis may be treated with oral oxytetracycline alone or in combination with topical agents.
6) Rickettsial infections: Rocky Mountain spotted fever, typhus group, Q fever and Coxiella endocarditis and tick fevers.
7) Other infections: Stagnant loop syndrome. Psittacosis, brucellosis (in combination with streptomycin), cholera, bubonic plague, louse and tick-borne relapsing fever, tularaemia, glanders, melioidosis and acute intestinal amoebiasis (as an adjunct to amoebicides).
Oxytetracycline is an alternative drug in the treatment of leptospirosis, gas-gangrene and tetanus.
4.2 Posology and method of administration
Posology:
Therapy should be continued for at least three days after symptoms have subsided.
All infections due to Group A beta-haemolytic streptococci should be treated for at least 10 days.
Adults (including the elderly) and children over 12 years: The minimum recommended dosage is 250 mg every six hours. Therapeutic levels are attained more rapidly by the administration of 500 mg initially, followed by 250 mg every six hours. For severe infections, the dosage may be increased to 500 mg every six hours.
Children under 12 years: Oxytetracycline is contra-indicated in children under the age of 12 years.
Elderly: Usual adult dose. Caution should be observed as subclinical renal insufficiency may lead to drug accumulation.
Renal impairment: In general, tetracyclines are contraindicated in renal impairment and the dosing recommendations only apply if use of this class of drug is deemed absolutely essential. Total dosage should be decreased by reduction of recommended individual doses and/or by extending time intervals between doses.
Dosage recommendations in specific infections:
Skin infections: Oxytetracycline 250-500mg daily in single or divided doses should be administered for at least 3 months in the treatment of acne vulgaris and severe rosacea.
Streptococcal infections: A therapeutic dose of oxytetracycline should be administered for at least 10 days.
Brucellosis: Oxytetracycline 500mg, four times daily in combination with streptomycin.
Sexually transmitted diseases: Oxytetracycline 500mg four times daily for 7 days is recommended in the following infections: uncomplicated gonococcal infections (except anorectal infections in man); uncomplicated urethral, endocervical or rectal infection caused by Chlamydia trachomatis; nongonococcal urethritis caused by Ureaplasma urealyticum.
Acute epididymal-orchitis caused by Chlamydia trachomatis, or Neisseria gonorrhoeae, Oxytetracycline 500mg four times daily for 10 days.
Primary and secondary syphilis: Oxytetracycline 500mg, four times daily for 15 days. Syphilis of more than a year’s duration, (latent syphilis of uncertain or more than a year’s duration, cardiovascular or late benign syphilis) except neurosyphilis, should be treated with Oxytetracycline 500mg, four times daily for 30days. Patient compliance with this regimen may be difficult so care should be taken to encourage optimal compliance. Close follow-up, including laboratory tests is recommended.
Method of administration
For oral administration
Oxytetracycline should be taken on an empty stomach i.e. one hour before or two hours after meals, since food, milk and some dairy products interfere with the absorption. If gastric irritation occurs, tablets should be taken with food. Tablets should be taken well before going to bed.
4.3 Contraindications
• Hypersensitivity to the active substance, any of the tetracycline or any of the excipients listed in section 6.1
• Renal or hepatic impairment
• Systemic lupus erythematosus
• Children under 12 years
• Pregnancy and breastfeeding women
• Porphyria
• Patients receiving vitamin A or retinoid therapy.
4.4 Special warnings and precautions for use
Tetracycline drugs may cause permanent tooth discoloration (yellow-grey-brown), if administered during tooth development, in the last half of pregnancy and in infancy up to twelve years of age. Enamel hypoplasia has also been reported. This adverse reaction is more common during long-term use of the drug but has been observed following repeated short-term courses.
Absorption is adversely affected by milk, antacids and aluminium, calcium, iron, magnesium and zinc salts.
Tetracyclines depress plasma prothrombin activity, therefore reduced dosages of concurrent anticoagulants may be required.
Lower doses are indicated in cases of renal impairment to avoid excessive systemic accumulation and if therapy is prolonged serum level determinations are advisable.
Special care should be taken when treating the elderly or patients receiving potentially hepatotoxic drugs.
High doses of tetracyclines have been associated with a syndrome involving fatty liver degeneration and pancreatitis.
Care is advisable in patients with myasthenia gravis.
Treatment should cease if symptoms of benign intracranial hypertension (e.g. headache and visual disturbance) develop.
Photosensitivity reactions may occur in hypersensitive persons and such patients should be warned to avoid direct exposure to natural or artificial sunlight and to discontinue therapy at the first sign of skin discomfort.
In long-term therapy, periodic laboratory evaluation of organ systems, including haematopoietic, renal and hepatic studies should be performed.
The use of antibiotics may occasionally result in the overgrowth of nonsuceptible organisms including Candida. Constant observation of patients is essential. If a resistant organism appears, the antibiotic should be discontinued and appropriate therapy instituted.
When treating venereal disease, where co-existent syphilis is suspected, proper diagnostic procedures should be utilised. In all such cases monthly serological tests should be made for at least four months.
Important information regarding the ingredients of this medicine
This medicine contains sucrose and glucose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.
This medicine also contains tartrazine aluminum lake (E102) which may cause allergic reactions.
4.5 Interactions with other medicinal products and other forms of interaction
The absorption of oxytetracycline may be impaired by the concomitant administration of antacids such as aluminium, calcium or magnesium, oral iron or zinc preparations. Allow two to three hours between doses of oxytetracycline and antacids.
Antidiarrhoeal preparations such as kaolin-pectin and bismuth subsalicylate hinder absorption of tetracyclines.
Oxytetracycline may potentiate action of some anti-coagulants.
Since bacteriostatic drugs may interfere with the bactericidal action of penicillin, it is advisable to avoid giving Oxytetracycline in conjunction with penicillin.
The nephrotoxic effects of tetracyclines may be exacerbated by coadministration of diuretics, methoxyflurane or other drugs known to be nephrotoxic.
Dairy products and food may interfere with absorption.
Oxytetracycline may increase hypoglycaemic effects of insulin and sulphonylureas in patients with diabetes mellitus. (See section 4.8)
Benign intracranial hypertension has been reported following the concomitant use of tetracyclines and vitamin A or retinoid and therefore concurrent use in contraindicated.
4.6 Pregnancy and lactation
Pregnancy
The product should not be used in pregnancy unless absolutely essential.
Animal studies have shown that tetracyclines cross the placenta and may have toxic effects on foetal tissues, particularly on skeletal development (see section 4.4).
The use of tetracycline compounds during pregnancy has been associated with reports of maternal liver toxicity.
Use in newborns, infants & Children: All tetracyclines form stable calcium complex in any bone forming tissue.
A decrease in fibula growth rate has been observed in premature infants given oral tetracycline in doses of 25 mg/kg every 6 hours. This reaction was reversed when drug was discontinued.
Breast-feeding
Tetracyclines are also excreted in breast milk and are therefore contraindicated in nursing mothers.
4.7 Effects on ability to drive and use machines
None known.
4.8 Undesirable Effects
Very common (1/10); common (1/100 to <1/10); uncommon (1/1,000 to <1/100); rare (1/10,000 to <1/1,000); very rare (<1/10,000); Frequency not known (cannot be estimated from the available data).
Blood and lymphatic disorders:
Frequency not known: Haemolytic anaemia, thrombocytopenia, neutropenia, eosinophilia.
Endocrine disorders:
Frequency not known: brown-black microscopic discoloration of thyroid tissue in use over prolonged periods (No abnormalities of thyroid function are known to occur).
Nervous system disorders:
Frequency not known: Bulging fontanelles in infants, benign intracranial hypertension.
(Treatment should cease if evidence of raised intracranial pressure develops.)
Cardiac disorders:
Frequency not known: Pericarditis.
Gastrointestinal disorders:
Rare: oesophagitis, oesophageal ulceration
(Reported in patients receiving capsule and tablet forms of drugs in the tetracycline class. Most of these patients took medication immediately before going to bed.)
Frequency not known: Gastrointestinal irritations giving rise to nausea, abdominal discomfort, vomiting, diarrhoea, anorexia, dysphagia (If gastric irritation occurs, tablets should be taken with food.). Pseudomembranous colitis, intestinal overgrowth of resistant organisms (Candida albicans, in particular), may occur and cause glossitis, rectal and vaginal irritation and inflammatory lesions (with candidial overgrowth) in the anogenital regions. Similarly, resistant staphylococci may cause enterocolitis. Tooth discolouration, pancreatitis.
Hepatobiliary system disorders:
Frequency not known: Hepatotoxicity (hepatitis, jaundice and hepatic failure), fatty liver degeneration.
Skin and subcutaneous tissue disorders:
Uncommon: Exfoliative dermatitis
Rare: Macropapular and erythematous rashes, photo-erythema, photosensitivity (Patients exposed to direct sunlight or ultraviolet light should be advised to discontinue treatment if any skin reaction occurs).
Hypersensitivity reactions: urticaria, angioneurotic oedema, anaphylaxis, anaphylactoid purpura, pericarditis, exacerbation of systemic lupus erythematosus.
Renal and urinary disorders:
Frequency not known: Renal dysfunction.
Reporting of Suspected Adverse Reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard
4.9 Overdose
There is no specific antidote to oxytetracycline. Over dosage may be treated with gastric lavage and/or the administration of antacids or milk, is recommended.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Oxytetracycline is bacteriostatic antibiotic with a broad spectrum of activity against a large number of gram positive and gram negative bacteria and also some antiprotozoal properties.
The product acts by interfering with bacterial protein synthesis.
5.2 Pharmacokinetic properties
Oxytetracycline is incompletely and irregularly absorbed from the gastrointestinal tract.
The degree of absorption is diminished by the soluble salts of divalent and trivalent metals, with which tetracyclines form stable complexes and to a variable degree by milk and food. Plasma concentrations will depend upon the degree of absorption.
It is recommended that tetracyclines should be give before food. A dose of 500mg every 6 hours by mouth is reported to produce steady-state plasma concentrations of 3 to 4pg per ml.
In the circulation, tetracyclines are bound to plasma proteins in varying degrees, but reported values differ considerably: from about 20 to 40% for oxytetracycline.
Oxytetracycline appears in the milk of nursing mothers where concentrations may be 60% or more of those in the plasma. Oxytetracycline diffuses across the placenta and appears in the foetal circulation at concentrations of about 25 to 75% of those in the maternal blood.
Tetracyclines are widely distributed throughout the body tissues and fluids. Only small amounts appear in saliva, tears and intraocular fluids and lung.
Oxytetracycline is retained at sites of new bone formation and recent calcification and in developing teeth.
The tetracyclines are excreted in the urine and in the faeces. Renal clearance is by glomerular filtration.
Since there is some enterohepatic reabsorption complete elimination is slow. Considerable quantities occur in the faeces after administration by mouth. Oxytetracycline is excreted in the bile where concentrations five to twenty five times those in plasma can occur.
5.3 Preclinical safety data
Not applicable
6. PHARMACEUTICAL PARTICULARS
6.1. List of excipients
Tablet core:
Cellulose microcrystalline Alginic acid Povidone
Magnesium Stearate Stearic acid Maize starch
Tablet coat:
Sandarac Sucrose Glucose Purified talc
Tartrazine aluminium lake (E102)
Titanium dioxide (E171)
Povidone
Sodium benzoate Carnauba wax
6.2. Incompatibilities
Not applicable.
6.3. Shelf Life
36 months.
6.4. Special Precautions for Storage
Glass bottle: Store in a cool dry place.
Blister packs: Store in a cool dry place. Store in the original package.
6.5 Nature and Contents of Container
Amber glass bottle and tin plate screw cap with aluminium faced pulpboard. The ullage is filled with cotton wool.
Pack sizes: 1000, 112, 56, 28
Blister packs comprising of 250 micron PVC and 20 micron Aluminium foil Pack sizes: 10, 14,28, 30, 56, 84, 100 (Not all pack sizes may be marketed)
6.6. Instruction for Use/Handling
Not applicable.
7. MARKETING AUTHORISATION HOLDER
Bristol Laboratories Ltd Unit3 , Canalside,
Northbridge Road Berkhamsted Herts HP4 1EG United Kingdom
8.
MARKETING AUTHORIZATION NUMBER(S)
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
9.
10
16th February 2005
DATE OF REVISION OF THE TEXT
24/03/2016