Trade Name of the Medicinal Product
Doxycycline Capsules 50 mg (Vibramax 50)
Qualitative and Quantitative Composition
Doxycycline base (as doxycycline hyclate Ph. Eur.) 50 mg
Hard gelatin capsules, containing spherical yellow to yellowish coated microgranules,
intended for oral administration to human beings.
As a bacteriostatic antibiotic, doxycycline is clinically effective in the treatment of a variety
of infections caused by a wide range of gram-negative and gram-positive bacteria, as well as
certain other micro-organisms.
Its principal indications are the following:
Pneumonia : respiratory tract infections : pneumonia and other lower respiratory tract
infections due to susceptible strains of Streptococcus pneumoniae, Haemophilus influenzae,
Klebsiella pneumonia and other organisms.
Mycoplasma pneumoniae pneumonia.
Treatment of chronic bronchitis, sinusitis.
Genito-urinary tract infections : cystitis, urethritis, pyelonephritis, caused by susceptible
strains of Escherichia coli, Neisseria gonorrhoeae, the Klebsiella-Enterobacter group,
Staphylococcus species and Chlamydia trachomatis. A single large dose of doxycycline has
effectively treated acute gonococcal anterior urethritis in the adult male. However, a more
extended therapy elicited the highest cure rates.
Soft tissue infections: infected traumatic and postoperative wounds, furunculosis, impetigo,
cellulitis, abscess and paronychia, caused by susceptible strains of the Klebsiella-
Enterobacter group, as well as susceptible strains of Staphylococcus aureus, Streptococcus
species, Escherichia coli and Staphylococcus albus.
Doxycycline treatment of soft tissue infections should always be carried out in conjunction
with any necessary indicated surgical procedures.
Dermatological infections: Acne vulgaris and Acne conglobata.
As doxycycline is one of the tetracycline group of antibiotics, it may be expected to be
useful in the treatment of infections which respond to other tetracyclines such as:
Gastro-intestinal infections: caused by susceptible strains of such organisms such as
Shigella species, Salmonella species, Entamoeba histolytica and enteropathogenic
Ophthalmic infections : caused by susceptible strains of Staphylococci, Gonococci and
Doxycycline is indicated for the treatment of inclusion conjunctivitis either alone or in
combination with topical agents. Doxycycline is also suitable in the treatment of trachoma.
However, the infectious agent is not eliminated on all occasions, as tested by
Miscellaneous : trigonitis and prostatitis caused by Proteus species. Psittacosis, certain other
infections caused by susceptible strains of Bacteroides species, Listeria species, Rickettsia
species, Yersinia species, Brucella species (in combination with streptomycin) and
Bordetella pertussis, Calymmato-bacterium granulomatis, Spirochaetes (Treponema
species), Bacillus anthracis, Neisseria meningitis and Clostridum welchii.
Doxycycline may be a useful adjunct to amoebicides in the treatment of acute intestinal
Posology and Method of Administration
The recommended adult dose of doxycycline is 200 mg on the first day of treatment (which
can be given as a single dose or divided into two 100 mg doses at a 12 hour interval)
followed by a 100 mg/day maintenance dose.
For more severe infections, especially chronic urinary tract infections, a daily dose of 200
mg should be administered throughout the period of treatment.
Use in children over 12 years of age
The recommended dosage schedule for children weighing 50 kg or less, is 4 mg/kg of body
weight on the first day of treatment (given as a single dose or divided into two equal doses
with a 12 hour interval), followed by 2 mg/kg of body weight on subsequent days.
For more severe infections up to 4 mg/kg of body weight may be used daily. For children
over 50 kg the usual adult dose should be used.
Use in the elderly
Doxycycline may be prescribed in the usual dose with no special precautions. No dosage
adjustment is necessary in the presence of renal impairment.
Conventional-capsule forms of the tetracycline class of drugs are liable to cause oesophageal
irritation and ulceration. Administration of adequate amounts of fluid is therefore
recommended to combat this problem. If, however, gastric irritation does occur, doxycycline
capsules can be given with food or milk. The absorption of doxycycline is not markedly
influenced by simultaneous ingestion of food or milk.
If the recommended dosage is exceeded, an increase in the incidence of side effects may
ensue. Treatment should be continued for a least 24 hours beyond the period when
symptoms and fever have abated.
In the specific case of Streptococcal infections, treatment should be continued for 10 days in
order to prevent the development of glomerulonephritis or rheumatic fever.
Acne vulgaris: in the treatment of Acne vulgaris the recommended dose is 50 mg daily with
food or fluid. Duration of treatment will vary from 6 to 12 weeks or longer dependent upon
Acute gonococcal infections in the adult female: a dosage schedule of 100 mg twice a day to
be continued until a cure is effected.
Acute epididymo-orchitis caused by Chlamydia trachomatis or Neisseria gonorrhoeae: 100
mg twice daily for 10 days.
Primary and secondary syphilis: a recommended daily dosage of 300 mg in divided doses to
be administered for a least 10 days.
Typhus of the louse-borne variety has been successfully treated with a single dose of 100 to
200 mg depending on the severity of infection.
Known hypersensitivity to tetracyclines.
Special Warnings and Precautions for Use
Tetracyclines may cause a yellow to brown discoloration of the teeth and enamel hypoplasia
in children and therefore, doxycycline should only be administered if considered essential to
children under 12 years of age.
Tetracyclines have been reported to cause photosensitivity and allergic skin reactions.
Patients should be advised to avoid direct exposure to natural or artificial sunlight and that
treatment should be discontinued at the first signs of skin discomfort.
The use of antibiotics may occasionally result in over-growth of nonsusceptible organisms.
Constant observation of the patient is essential. If a resistant organism appears, the
antibiotic should be discontinued and appropriate therapy instituted.
Patients known to have, or suspected to have, achlorhydria should not be prescribed
When treating venereal disease when co-existent syphilis is suspected, proper diagnostic
procedures, including dark-field examinations, should be utilized. In such cases monthly
serological tests should be performed for at least four months.
Infection due to group A beta-haemolitic streptococci should be treated for at least ten
Interactions with other Medicaments and other forms of Interaction
Patients taking doxycycline should not be simultaneously ingesting antacids containing
magnesium, aluminium or calcium salts as these impair absorption.
Since bacteriostatic drugs may interfere with the bactericidal action of penicillin, it is
advisable to avoid giving doxycycline in conjunction with penicillin.
In long term treatment, the tetracyclines depress plasma prothrombin activity, therefore
reduced dosages of concurrent anti-coagulants may be required.
Barbiturates, carbamazepine, and phenytoin decrease the half-life of doxycycline. The
concurrent use of tetracyclines and methoxyflurane has been reported to result in fatal renal
Although not reported for doxycycline, a few cases of pregnancy or breakthrough bleeding
have been attributed to the concurrent use of tetracycline or oxytetracycline with oral
Studies indicate that doxycycline at usual dosages in patients with renal impairment does not
lead to excessive accumulation of the antibiotic within the body.
Pregnancy and Lactation
Doxycycline is contra-indicated in pregnancy.
Results of animal studies indicate that tetracyclines cross the placenta, are found in foetal
tissues and can have toxic effects on the developing foetus (often related to retardation of
skeletal development). Evidence of embryotoxicity has also been noted in animals treated
early in pregnancy.
Tetracyclines are present in the milk of lactating women who are taking drugs of this class
and should therefore be avoided in nursing mothers.
Effects on Ability to Drive and Use Machines
Due to the fact that doxycycline is virtually completely absorbed, gastro-intestinal sideeffects are infrequent.
Patients receiving tetracyclines are known, however, to exhibit the following adverse
Gastro-intestinal : diarrhoea, nausea, vomiting and anorexia may occur and, as with all
antibiotics, overgrowth of resistant organisms may cause glossitis, stomatitis or
Skin: maculopapular and erythematous rashes. Exfoliative dermatitis has been reported but
is uncommon. Photosensitivity is discussed in the "warnings" section.
Hypersensitivity reactions : anaphylaxis, anaphylactoid purpura, angioneurotic oedema,
urticaria, pericarditis and exacerbation of systemic lupus erythematosus.
Bulging fontanelles in infants and benign intracranial hypertension in adults have been
reported. Treatment should be withdrawn if evidence of raised intracranial pressure
develops. These symptoms disappeared rapidly when the drug was discontinued.
Blood: thrombocytopenia, haemolytic anaemia, eosinophilia and neutropenia have all been
reported with tetracyclines.
When given over prolonged periods, tetracyclines have been reported to produce brownblack microscopic discoloration of thyroid tissue. No abnormalities of thyroid function are
known to occur.
Acute overdosage with antibiotics is rare. There is no specific antidote but in the event of
overdosage, gastric lavage plus appropriate supportive treatment is indicated.
As an antibiotic, doxycycline exerts its antimicrobial effect by the inhibition of protein
synthesis and is considered to be primarily bacteriostatic.
Doxycycline is clinically effective in the treatment of a variety of infections caused by a
wide range of gram-negative and gram-positive bacteria, as well as certain other microorganisms.
- absorption is rapid (effective concentrations are attained as from the first hour), and the
peak serum concentration occurs after 2 to 4 hours.
- almost all of the product is absorbed in the upper part of the digestive tract.
- absorption is not modified by administration with meals, and milk has little effect.
In adults, an oral dose of 200 mg results in :
- a peak serum concentration of more than 3 µg/ml
- a residual concentration of more than 1 µg/ml after 24 hours
- a serum half-life of 16 to 22 hours
- protein binding varying between 82 and 93% (labile binding).
Intra- and extracellular diffusion is good.
With usual dosages, effective concentrations are found in the ovaries, uterine tubes, uterus,
placenta, testicles, prostate, bladder, kidneys, lung tissue, skin, muscles, lymph glands, sinus
secretions, maxillary sinus, nasal polyps, tonsils, liver, hepatic and gallbladder bile,
gallbladder, stomach, appendix, intestine, omentum, saliva and gingival fluid. Only small
amounts are diffused into the cerebrospinal fluid.
The antibiotic is concentrated in the bile. About 40% of the administered dose is eliminated
in 3 days in active form in the urine and about 32% in the faeces. Urinary concentrations are
roughly 10 times higher than plasma concentrations at the same time. In the presence of
impaired renal function, urinary elimination decreases, faecal elimination increases, and the
half-life remains unchanged. The half-life is not affected by haemodialyis.
Preclinical Safety Data
List of Excipients
Sucrose and maize starch microgranules
Gelatin (capsule shell)
Colourants E171, E132, E104, E172 (capsule shell)
Special Precautions for Storage
Nature and Contents of Container
Doxycycline capsules are packed in blister packs (200 micron rigid, opaque white polyvinyl
chloride and 20 micron aluminium).
Doxycycline capsules 50 mg: boxes of 2, 28 and 56 capsules.
Instruction for Use/Handling
See part 4.2 "Posology and method of administration".
Marketing Authorisation Holder
Trinity Pharmaceuticals Limited
27 - 37 St George's Road
Marketing Authorization Number
Date of First Authorisation/Renewal of Authorisation
20 November 1995.
Date of (Partial) Revision of the Text