Source: Marketing Authorisation Holder Revision Year: 2023 Publisher: Accord-UK Ltd (Trading style: Accord), Whiddon Valley, Barnstaple, Devon, EX32 8NS
Tetracyclines depress plasma prothrombin activity; therefore reduced dosages of concurrent anticoagulants may be required.
Tetracycline drugs may cause permanent tooth discolouration (yellow-greybrown), if administered during tooth development, in the last half of pregnancy and in infancy up to twelve years of age (see sections 4.3, 4.6 and 4.8). 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 tetracycline 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 (see section 4.8). Constant observation of the patients is essential. If a resistant organism appears, the antibiotic should be discontinued and appropriate therapy instituted.
Diarrhoea, particularly if severe, persistent and/or bloody, during or after treatment (including several weeks after treatment) with Tetracycline tablets, may be symptomatic of Clostridium difficile-associated disease (CDAD). CDAD may range in severity from mild to life threatening, the most severe form of which is pseudomembranous colitis (see section 4.8). It is therefore important to consider this diagnosis in patients who develop serious diarrhoea during or after treatment with Tetracycline tablets. If CDAD is suspected or confirmed Tetracycline tablets should be stopped immediately and appropriate therapy initiated without delay. Anti-peristaltic drugs are contraindicated in this clinical situation.
In longterm 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 tetracycline in general is contraindicated in renal impairment due to excessive systemic accumulation. They should not be used with penicillins and they should not be discontinued if supra-infection occurs. Tetracyclines should also be used with caution in patients with hepatic impairment or those receiving drugs which may have hepatotoxic effects; high doses should be avoided.
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.
SLE (systemic lupus erythematosus) can be exacerbated by the use of tetracyclines.
Care is advised when administered to patients with myasthenia gravis.
Sunset yellow: Tetracycline tablets contain sunset yellow (E110), which can cause allergic-type reactions.
Sodium: This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.
The absorption of tetracycline from the gastrointestinal tract is impaired by the concomitant administration of di and trivalent cations such as iron, calcium, aluminium, magnesium, bismuth and zinc salts. Administration of medicinal products containing these cations and tetracycline should be maximally separated by at least two to three hours. The following should be avoided when taking tetracycline: antacids, bismuth containing ulcer-healing drugs, drugs such as quinapril tablets which contain magnesium carbonate and didanosine which contains calcium and magnesium excipients.
Absorption of tetracycline is impaired by food, milk, and milk products.
Since tetracycline has been shown to depress plasma prothrombin activity, patients who are on anticoagulant therapy may require a downward adjustment of their anticoagulant dosage. Tetracycline may prolong the action of coumarin anticoagulants.
Plasma-atovaquone concentration is reduced by tetracycline.
There is a possible increased risk of benign intracranial hypertension with tetracyclines and retinoids (acitretin, isotretinoin, tretinoin). Concomitant use should be avoided.
Antidiarrhoeal preparations such as kaolin-pectin and bismuth subsalicylate hinder absorption of tetracyclines.
Combination of tetracyclines with diuretics may be detrimental to renal function and may aggravate nephrotoxicity by volume depletion.
Since bacteriostatic drugs may interfere with the bactericidal action of penicillin, it is advisable to avoid giving tetracycline in conjunction with penicillin.
A few cases of pregnancy or breakthrough bleeding have been attributed to the concurrent use of tetracycline 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 tetracycline therapy has been combined with methoxyflurane.
Tetracycline may increase the hypoglycaemic effects of insulin and sulfonylureas in patients with diabetes mellitus.
The absorption of tetracycline may be reduced by the concomitant administration of sucralfate. Separating administration should be considered.
Tetracycline may cause an increase in serum lithium levels.
Tetracycline may cause an increase in serum digoxin levels.
Tetracycline may cause an increase the risk of methotrexate toxicity. Regular monitoring of toxicity is necessary when taken concurrently.
Absorption of tetracycline is impaired by strontium ranelate (manufacturer of strontium ranelate advises avoid concomitant use).
Absorption of tetracycline is possibly reduced by colestipol and colestyramine.
Increased risk of ergotism when tetracycline given with ergotamine and methysergide.
Tetracycline may be deposited in deciduous and permanent teeth giving permanent discolouration. It should not be used during pregnancy or lactation.
Not to be used in pregnancy unless essential to the patient’s welfare.
Tetracyclines cross the placenta and may have toxic effects on foetal tissues, particularly on skeletal development, (see sections 4.3, 4.4 and 4.8).
The use of tetracycline compounds during pregnancy has been associated with reports of maternal liver toxicity.
If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be appraised of the potential hazard to the foetus.
Tetracyclines are also excreted in breast milk and are therefore contraindicated in nursing mothers.
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.
None known.
The following convention has been utilised for the classification of frequency. Very common (≥1/10); common (≥1/100 and <1/10); uncommon (≥1/1000 and <1/100); rare (≥1/10,000 and <1/1000); very rare (<1/10,000); Frequency not known (cannot be estimated from the available data).
Not known: overgrowth of resistant organisms (Candida albicans, in particular); this may cause glossitis, stomatitis, pseudomembranous colitis (Clostridium difficile overgrowth), enterocolitis (caused by resistant staphylococci), rectal and vaginal irritation, inflammatory lesions (with candidial overgrowth) in the anogenital regions (see section 4.4)
Rare: haemolytic anaemia, thrombocytopenia, neutropenia, eosinophilia, agranulocytosis, aplastic anaemia.
Not known: hypersensitivity reactions including Stevens-Johnson syndrome, angioedema, toxic epidermal necrolysis, urticaria, anaphylaxis, anaphylactoid purpura, pericarditis, and exacerbation of systemic lupus erythematosus (see sections 4.3 and 4.8), fixed drug eruptions, exfoliative dermatitis.
Not known: brown-black microscopic discolouration of thyroid tissue. No abnormalities of thyroid function are known to occur.
Not known: headache.
Not known: visual disturbances, permanent visual loss.
Not known: bulging fontanelles in infants; benign intracranial hypertension in juveniles and adults (see section 4.3). Presenting features were headache, dizziness, tinnitus and visual disturbances including blurring of vision, scotomata and diplopia. Treatment should cease if evidence of raised intracranial pressure develops.
Rare: dysphagia, oesophagitis and oesophageal ulceration (most of these patients took medication immediately before going to bed)
Not known: gastrointestinal irritations, nausea, abdominal discomfort, vomiting, diarrhoea, anorexia, pancreatitis, permanent tooth discolouration and enamel hypoplasia in children (see sections 4.3, 4.4 and 4.6). Tooth discolouration has also been seen in adults. If gastric irritation occurs, tablets should be taken with food.
Rare: transient increases in liver function tests, hepatitis, jaundice, hepatic failure.
Not known: hepatotoxicity associated with fatty liver.
Not known: erythematous and maculo-papular rashes, photosensitivity (Patients exposed to direct sunlight or ultraviolet light should be advised to discontinue treatment if any skin reaction occurs), pruritis, bullous dermatoses, skin discolouration.
Not known: increased muscle weakness in patients with myasthenia gravis (see section 4.4).
Rare: acute renal failure, nephritis.
Not known: raised serum urea, renal dysfunction, especially in patients with pre-existing renal impairment.
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; website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
None known.
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