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What are tetracyclines?

Tetracyclines are oral antibiotics often used to treat skin diseases. There has been over 50 years’ experience with these medications, which were originally derived from soil bacteria Streptomyces aureofaciens.

The original base medicines, chlortetracycline, tetracycline and oxytetracycline, have been replaced by products that are better absorbed and more lipophilic, with excellent tissue distribution. These include:

  • Doxycycline
  • Lymecycline
  • Minocycline

Doxycycline is the most commonly prescribed tetracycline.

Chemically modified tetracyclines are under development to reduce antibiotic activity and to increase their non-antibiotic, anti-inflammatory effect.

What are tetracycline and its derivatives used for?

Tetracyclines are broad spectrum antibiotics often used to treat skin, chest, urethral, and pelvic infections. Doxycycline is indicated in a wide range of infections including syphilis, Lyme disease, Q fever, Rocky Mountain spotted fever, and plague. It is also widely used for malaria prophylaxis.

Doxycycline is also effective at controlling non-infectious, inflammatory skin and mucosal diseases, including:

  • Acne
  • Rosacea
  • Perioral dermatitis
  • Hidradenitis suppurativa
  • Recurrent aphthous stomatitis
  • Bullous pemphigoid
  • Granulomatous disorders such as sarcoidosis
  • Pyoderma gangrenosum
  • Sweet disease
  • Pityriasis lichenoides chronica

It is important to note that the use of tetracyclines does not increase Staphylococcus aureus resistance (see MRSA).

How do tetracyclines work?

As antibiotics, tetracyclines interfere with protein synthesis of susceptible bacteria.

They are also anti-inflammatory agents.

  • They inhibit matrix metalloproteinases (MMPs), hydrolases and phospholipase A2 — these enzymes are active in dermalinflammatory skin disorders.
  • They reduce production of pro-inflammatory cytokines such as TNF-a, IL-1B, and IL-6.
  • They are antioxidants, reducing free radical production and nitric oxide.
  • They inhibit angiogenesis and granuloma formation.

What is the usual dose?

The antibiotic dose of doxycycline is 100 mg once or twice daily. It should be taken while upright, with plenty of water.

Lower doses of doxycycline have been shown to be effective in rosacea (20 mg twice daily or 40 mg once daily). The effect of low-dose doxycycline in other skin disorders is unknown, and is quite common for an antibiotic dose to be prescribed.

For how long are tetracyclines taken?

Infections are treated for 7 to 28 days, depending on the condition being treated.

Inflammatory disorders take several weeks or months to respond to tetracyclines such as doxycycline. They are often prescribed for months or years for inflammatory skin disorders. They are not curative for these conditions.

There’s a lag period of one to three weeks between the change in dosage and its effect on skin. If the skin problem becomes worse, return to the previous higher dosage and continue on it or as advised by your doctor.

What are the side effects and risks of tetracycline and its derivatives?

Tetracyclines must not be taken by pregnant or breast-feeding women, or by children under 12 years, because they discolour growing teeth and may cause enamel hypoplasia (malformed permanent teeth). Staining of permanent teeth is usually temporary but can persist for long periods. They can also affect bones.

Doxycycline is usually tolerated very well, particularly in subantibiotic dose.  Allergy can occur, but it’s rare. There are some important precautions.

  • It must be taken when upright and with copious water, to reduce oesophagitis. Wait about an hour before lying down
  • Patients should protect skin and nails from sun exposure, as it is photosensitising and can cause unexpected sunburn
  • It can cause nausea, vomiting and diarrhoea; it is better tolerated when taken after food than on an empty stomach
  • Women prone vulvovaginal candida infection (thrush) with broad-spectrum antibiotics should consider prophylactic treatment with intermittent topical or systemic azole antifungal agent

Minocycline has an increased risk of severe adverse effects compared to doxycycline, so it best to avoid minocycline as a first-line agent. These include:

  • Drug hypersensitivity syndrome
  • Autoimmune reactions
  • Dizziness and headache
  • After prolonged use, blue pigmentation of skin and nails

Minocycline is less likely than doxycycline to cause photosensitivity.

Drug interactions

Important drug interactions of tetracycline and its derivatives include:

  • Risk of raised intracranial hypertension with systemic retinoids (acitretin, isotretinoin, alitretinoin)
  • Reduced bioavailability of tetracyclines with iron, aluminium, magnesium, calcium, rifampicin, celestipol and anticonvulsants
  • Increased renal toxicity with diuretics
  • May increase lithium concentrations, which can lead to toxicity

Effect on contraceptives

There is little evidence that tetracyclines reduce the efficacy of the oral contraceptive pill unless they cause gastrointestinal upset. However, to be absolutely safe, extra precautions should be taken, particularly in the first four weeks of starting the antibiotics. Discuss this with your doctor.

If you develop side affects, advise your doctor. You may need to stop taking the tetracycline or change brand.

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