Oxytetracycline Tablets Bp 250mg
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Oxytetracycline Tablets BP 250 mg
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains oxytetracycline dihydrate 250 mg For excipients, see 6.1.
3 PHARMACEUTICAL FORM
Tablet, coated.
Yellow, deep convex, sugar, coated tablets.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Oxytetracycline tablets are indicated in the treatment of infections caused by oxytetracycline-sensitive organisms. These include chronic bronchitis, pneumonia, urinary tract infections, brucellosis, pertussis, rickettsial fevers and psittacosis.
4.2 Posology and method of administration
Oxytetracycline should be given one hour before or two hours after meals, since food and some dairy products interfere with absorption. Therapy should be continued for up to three days after symptoms have subsided.
Route of administration: Oral.
Adults and children over 12: One tablet four times a day. This may be increased to 6 or 8 tablets daily in severe infections.
Children: Not recommended for children under 12 years
Elderly: Oxytetracycline tablets 250 mg should be used with caution in the treatment of elderly patients where accumulation is a possibility.
4.3 Contraindications
Oxytetracycline tablets are contraindicated in patients with chronic renal impairment/hepatic dysfunction, hypersensitivity to tetracyclines or any of the other ingredients in the formulation, Systemic Lupus Erythematosus (SLE), in children under the age of 12, patients receiving vitamin A or retinoid therapy and in lactation and throughout pregnancy.
Use of oxytetracycline in patients with renal impairment should be avoided because of the associated anti-anabolic effect caused, increased levels of plasma urea and further deterioration in renal function.
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.
The anti-anabolic action of tetracyclines may cause an increase in BUN. While this is not a problem in those with normal renal function, in patients with significantly impaired renal function, higher serum levels of oxytetracycline may lead to azotaemia, hyperphosphataemia and acidosis.
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.
The use of antibiotics may occasionally result in the overgrowth of nonsusceptible organisms including Candida. Constant observation of the patients is essential. If a resistant organism appears, the antibiotic should be discontinued and appropriate therapy instituted.
In long-term therapy, periodic laboratory evaluation of organ systems, including haematopoietic, renal and hepatic studies should be performed.
High doses of tetracyclines have been associated with a syndrome involving fatty liver degeneration and pancreatitis.
The use of tetracyclines in general is contraindicated in renal impairment due to excessive systemic accumulation. Tetracyclines should be administered with caution in patients with hepatic impairment or those receiving potentially hepatotoxic drugs; this is of particular relevance to the elderly group of patients. High doses should be avoided.
Care is advised when administering to patients with myasthenia gravis.
Photosensitivity reactions may occur in hypersensitive persons and such patients should be warned to avoid direct exposure to natural or artifical sunlight and to discontinue therapy at the first sign of skin discomfort.
Tetracyclines should not be used with penicillins. Bulging fontanelles in infants and benign intracranial hypertension in adults has been reported. Treatment should cease if evidence of raised intracranial pressure develops.
Prolonged use of an anti-infective agent may result in the development of superinfection due to micro-organisms resistant to the anti-infective. Crossresistance between tetracyclines may develop in micro-organisms and crosssensitisation in patients.
4.5 Interaction with other medicinal products and other forms of interaction
Antacids: The absorption of oxytetracycline is impaired by the concomitant administration of calcium, magnesium, and particularly aluminium salts commonly used as antacids. Allow two to three hours between doses of oxytetracycline and antacids. Iron salts taken orally and zinc salts impair absorption of oxytetracycline and vice-versa.
Dairy products: Dairy products such as milk may also impair absorption.
Anticoagulants: Since oxytetracycline has been shown to depress plasma prothrombin activity, patients who are on anticoagulant therapy may require a downward adjustment of their anticoagulant dosage. Tetracyclines may prolong the action of coumarin anticoagulants (such as warfarin) and may themselves delay coagulation. Indandione derivative phenindione can also alter the International Normalised Ratio (INR).
ACE Inhibitors and Angiotensin-11 Antagonists: quinapril tablets containing magnesium carbonate as an excipient in the formulation reduce absorption of tetracyclines.
Adsorbents: Antidiarrhoeal preparations such as kaolin-pectin and bismuth subsalicylate hinder absorption of tetracyclines.
Combination of tetracyclines with diuretics may be detrimental to renal function.
Oestrogens and Progestogens: There have been reports that the reliability of combined oral contraceptives may be reduced when oxytetracycline is administered concomitantly. Extra precautions against conceiving are therefore advised in any cycle in which oxytetracycline is given. (Refer also to Section
4.6 Pregnancy & Lactation.) A few cases of pregnancy or breakthrough bleeding have been attributed to the concurrent use of oxytetracycline with oral contraceptives and alternative contraceptive advice should be sought where necessary
There have been reports of nephrotoxicity (increased blood urea nitrogen and serum creatinine) and death in some cases when oxytetracycline therapy has been combined with methoxyflurane.
Oxytetracycline may increase the hypoglycaemic effects of insulin and sulphonylureas in patients with diabetes mellitus.
Retinoids or vitamin A: Possible increased risk of benign intracranial hypertension with tetracyclines such as oxytetracycline and acitretin, isotretinoin and tretinoin. Avoid concomitant use.
Ulcer-healing drugs: tripotassium dicitratobismuthate and sucralfate reduce absorption of tetracycline such as oxytetracyclines.
Anaesthetics: Concurrent use of methoxyflurane with tetracyclines may increase its potential nephrotoxicity.
Digoxin: The bioavailability of digoxin may be increased by the concurrent use of tetracyclines.
Penicillins: Since bacteriostatic drugs like oxytetracycline may interfere with the bactericidal effect of penicillin in the treatment of meningitis or other situations where a rapid batericidal effect is necessary, it is best to avoid concurrent therapy.
Atovaquone: Concomitant use of atovaquone with tetracycline (and hence possibly oxytetracycline) leads to a reduced plasma concentration of atovaquone.
Ergotamine and ergometrine: There is an increased risk of ergotism if taken concurrently with oxytetracycline.
4.6 Fertility, pregnancy and lactation
Results of animal studies indicate that tetracyclines cross the placenta, are found in foetal tissues and can have toxic effects in the developing foetus (often related to retardation of skeletal development). Evidence of embryotoxicity has also been noted in animals treated early in pregnancy. Tetracyclines may also cause a yellow to brown discolouration of the teeth in the developing foetus or child. Tetracyclines are excreted in breast milk. Because tetracyclines may form unabsorbable complexes with calcium in breast milk, use is contraindicated during lactation. Tetracyclines should therefore not be used during pregnancy, lactation and in children under 12 years of age.
Oxytetracycline taken concomitantly may adversely interact with combined oral contraceptives (COCs). Patients taking broad-spectrum antibiotics such as oxytetracyclines should be advised about additional contraceptive precautions required during and after treatment as applicable. Advice on the exact duration of this alternative method is dependent on factors including the type of COC, length of treatment and stage of cycle.
Use in newborns, infants and children: All tetracyclines form a 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 25mg/kg every 6 hours. This reaction was reversed when drug was discontinued.
4.7 Effects on ability to drive and use machines
None reported.
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 and blood dyscrasias.
Endocrine disorders:
Frequency not known: Brown-black microscopic dicolouration of thyroid tissue in use over prolonged periods. (No abnormalities of thyroid function are known to occur).
Nervous system disorders:
Frequency not known: Myasthenia gravis. Bulging fontanelles in infants, benign intracranial hypertension. (Headache and visual disturbances may indicate increased intracranial pressure. Treatment should cease if evidence of raised intracranial pressure develops. This condition disappears rapidly upon cessation of treatment).
Cardiac disorders:
Frequency not known: Pericarditis.
Gastrointestinal disorders:
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, stomatitis, rectal and vaginal irritation, vaginitis and inflammatory lesions (with candidal overgrowth) in the anogenital regions. Similarly, resistant staphylococci may cause enterocolitis. Tooth discolouration, pancreatitis.
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).
Hepatobiliary system disorders:
Frequency not known: Hepatotoxicity (hepatitis, jaundice and hepatic failure), fatty liver degeneration.
Skin and subcutaneous tissue disorders:
Uncommon: Exfoliative dermatitis.
Frequency not known: Macropapular and erythematous rashes, photosensitivity (rarely), photo-erythema and skin discolouration. (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.
Congenital, familial and genetic disorders:
Occurrence of enamel hypoplasia has been reported.
4.9 Overdose
After oral ingestion the toxicity of tetracyclines is generally low. Symptoms and signs that may occur after overdose include transient fever, vomiting, melaena, jaundice and haematoma formation; transaminases may be elevated and prothrombin time prolonged.
In cases of overdosage, gastric lavage followed by appropriate symptomatic and supportive measures is required. Oral administration of milk or antacids may be used to reduce tetracycline absorption.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: General Antiinfectives for Systemic Use,
Tetracyclines - Oxytetracycline ATC Code: J01A A06
Oxytetracycline is a broad spectrum bacteriostatic antibiotic and acts by inhibiting protein synthesis by blocking the binding of aminoacyl TRNA (transfer RNA) to the MRNA (messenger RNA) ribosome complex. Reversible binding occurs primarily at the 30S ribosomal subunit of susceptible organisms. Bacterial cell wall synthesis is not inhibited.
5.2 Pharmacokinetic properties
Oxytetracycline is adequately but incompletely absorbed from the gastrointestinal tract. Approximately 58% of the drug is absorbed when the stomach is empty. Absorption is impaired by milk products, aluminium hydroxide gels, sodium bicarbonate, calcium and magnesium salts and iron preparations. The mechanism responsible for decreased absorption appears to be chelation and an increase in gastric pH.
The percentage of the unabsorbed drug increases as the dose increases. The drug is readily distributed to most body fluids including bile, sinus secretion, synovial, pleural, ascitic and gingival crevicular fluid. The concentration in gingival crevicular fluid may be 3-7 times the serum concentration. It tends to localize in bone, liver, spleen, tumours and teeth. Following a single oral dose, peak plasma concentrations are attained in 2 - 4 hours. The dose is frequently administered 2 - 4 times daily. Administration of 250 mg every 6 hours produces peak plasma concentration of approximately 3 pg/ml.
Oxytetracycline is excreted in urine and faeces, the primary route being the kidney. Since renal clearance is by glomerular filtration the excretion is significantly affected by the state of renal function.
5.3 Preclinical safety data
There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Talc
Maize starch Sodium lauryl sulphate Magnesium stearate
Coating
Talc
Kaolin heavy
Shellac
Sucrose
Dextrin
Gelatin
Nipasept sodium containing sodium methyl, sodium ethyl and sodium propyl hydroxybenzoate (E219, E215 and E217)
Titanium dioxide (E171)
Mastercote Yellow SP 2152 containing sodium benzoate (E211), sunset yellow FCF (E110), quinoline yellow (E104) and indigo carmine (E132)
6.2 Incompatibilities
None
6.3 Shelf life
As packaged for sale:
5 years - in plastic containers 2 years - in blister packs
6.4 Special precautions for storage
Keep out of the reach of children.
Store below 25°C, protect from light and moisture.
6.5 Nature and contents of container
1. Opaque plastic containers composed of polypropylene tubes and polyethylene made tamper evident or child resistant tamper evident closures with a packing inclusion of either standard polyether foam or polyethylene or polypropylene made filler in pack sizes of 9, 10, 14, 15, 20, 21, 28, 30, 50, 56, 84, 100, 250, 500 and 1000 tablets.
2. Blister packs of aluminium/opaque PVC. It is subsequently packed in printed boxboard cartons in pack sizes of 9, 10, 14, 15, 20, 21, 28, 30, 56 and 84 tablets.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
No specific instructions for use/handling
7 MARKETING AUTHORISATION HOLDER
Crescent Pharma Ltd
Units 3 and 4, Quidhampton Business Units
Polhampton Lane
Overton
Hampshire
RG25 3ED
United Kingdom
8 MARKETING AUTHORISATION NUMBER(S)
PL 20416/0217
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
22 April 2004
10
DATE OF REVISION OF THE TEXT
02/12/2011