Doxycycline Capsules Bp 50mg
SUMMARY OF PRODUCT CHARACTERISTICS
1. NAME OF THE MEDICINAL PRODUCT Doxylar/Doxycycline Capsules BP 50mg.
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each capsule contains Doxycycline Hyclate BP equivalent to 50mg doxycycline.
For the full list of excipients, see section 6.1.
3. PHARMACEUTICAL FORM
Capsule.
4. CLINICAL PARTICULARS
4.1. Therapeutic indications
Doxycycline is clinically useful in the treatment of a variety of infections caused by susceptible strains of gram-positive and gram-negative bacteria and certain other micro-organisms. These include:
Respiratory tract infections: Lower respiratory tract infections including pneumonia, due to susceptible strains of Haemophilus influenzae, Klebsiella pneumoniae, Streptococcus pneumoniae, and other organisms. Mycoplasma pneumoniae pneumonia. The treatment of chronic bronchitis and sinusitis.
Dermatological infections: Doxycycline can be used in the treatment of acne vulgaris in cases where antibiotic therapy is considered necessary.
Urinary infections: Infections caused by susceptible strains of Klebsiella, Enterobacter, Escherichia coli, Streptococcus faecalis and other organisms.
Sexually transmitted diseases: Infections including uncomplicated urethral, endocervical or rectal infections due to Chlamydia trachomatis, nongonococcal urethritis, caused by Ureaplasma urealyticum (t-mycoplasma). Doxycycline can also be used to treat chancroid and infections due to
Calymmatobacterium granulomatis or as an alternative drug for the treatment of gonorrhoea and syphilis.
As a member of the tetracycline group of antibiotics, Doxycycline may be useful in the treatment of infections due to other tetracycline-sensitive microorganisms such as:
Ophthalmic infections: Due to Haemophilus influenzae and susceptible strains of gonococci and staphylococci. Doxycycline is indicated in the treatment of trachoma. Inclusion conjunctivitis may be treated with oral doxycycline alone, or in combination with topical medication.
Rickettsial infections: Tick fevers, Q fever, rocky mountain spotted fever, coxiella endocarditis and typhus group.
Prophylaxis: Doxycycline is also indicated in the prophylactic treatment of leptospirosis, scrub typhus, travellers' diarrhoea (entero-toxigenic Escherichia coli) and malaria. Malarial prophylaxis is indicated in accordance with current guidelines due to the continuously changing problem of resistance.
Miscellaneous: Psittacosis, leptospirosis, cholera, meliodosis, other infections due to susceptible strains of yersinia species, brucella species (in combination with streptomycin), clostridium species, Francisella tularensis and chloroquine -resistant falciparum malaria.
4.2. Posology and method of administration
Adults: 200 mg on the first day (administered as a single dose or divided into two equal doses with a 12 hour interval) followed by a maintenance dose of 100 mg/day. For more severe infections (particularly chronic infections of the urinary tract) 200 mg should be given throughout the treatment.
Children over 12 years of age: Normal adult dose should be given.
Not recommended for use for children under 12 years of age (see contraindications).
Elderly: Doxycycline may be prescribed in the usual dose with no special precautions. No dosage adjustment is necessary in the presence of renal impairment.
It is recommended that patients over 70 years of age are specifically instructed regarding the administration of Doxycycline.
An adequate volume of fluid should be taken when administering Doxycycline capsules; this should preferably be taken in an upright position and not immediately before going to bed.
If gastric irritation occurs Doxycycline should be given with food or milk.
Treatment should be continued at least 24 to 48 hours after fever and symptoms have subsided. When used in Streptococcal infections, therapy should be continued for 10 days to prevent the development of rheumatic fever or glomerulo-nephritis.
Specific Infections: Acne vulgaris: 50 mg daily with food or fluid for 6 to 12 weeks.
Sexually transmitted diseases: for the treatment of uncomplicated gonococcal infections (except anorectal infections in males), uncomplicated urethral, endocervical or rectal infections caused by Chlamydia trachomatis, or nongonococcal urethritis caused by Ureaplasma urealyticum, 100 mg should be taken twice daily for 7 days.
For the treatment of acute epididymo-orchitis caused by Chlamydia trachomatis or Neisseria gonorrhoeae; 100 mg twice daily for 10 days.
For the treatment of primary and secondary syphilis: 300 mg a day in divided doses for at least 10 days.
Louse and tick - borne relapsing fevers: A single dose of 100 mg or 200 mg according to severity.
Chloroquine - resistant falciparum malaria: 200 mg to be taken daily for at least 7 days. A quick acting schizonticide such as quinine should be used in conjunction with Doxycycline because of the potential severity of the infection. Recommended dosages for quinine vary in different areas.
Prophylaxis: For the prevention of travellers' diarrhoea in adults: 200 mg on the first day of travel (administered as a single dose or as 100 mg every 12 hours), followed by 100 mg daily throughout the stay in the area.
For the prevention of scrub typhus: 200 mg to be taken as a single dose.
For the prevention of Leptospirosis: 200 mg to be taken once a week throughout the stay in the area and 200 mg at the end of the trip.
For the prophylaxis of malaria: 100mg daily in adults and children over the age of 12 years. Treatment should commence 1-2 days before travelling to a malarial area and continue daily whilst travelling in malarial areas. On leaving a malarial area the traveller should continue treatment for 4 weeks. To ensure appropriate chemoprophylaxis and for current information on geographical resistance patterns, the current guidelines or the Malarial Reference Laboratory should be consulted, details of which can be found in the current version of the British National Formula (BNF).
4.3. Contraindications
Doxycycline should not be administered to patients who have shown hypersensitivity to tetracyclines.
Doxycycline is also contra-indicated in pregnancy, infancy and childhood up to 12 years of age. The use of tetracyclines during tooth development may cause permanent discolouration of the teeth (yellow-grey-brown). This reaction is more common during long term use of the drug but has been observed following repeated short term courses. Enamel hypoplasia has also been reported.
As for other tetracyclines, Doxycycline forms a stable calcium complex in any bone-forming tissue. A decrease in the fibula growth rate has been observed in prematures given oral tetracycline in doses of 25mg/kg every 6 hours. This reaction was shown to be reversible when the drug was discontinued.
4.4. Special warnings and precautions for use
Doxycycline should be administered with caution to patients with hepatic impairment or those receiving potentially hepatotoxic drugs.
Care should be taken in the treatment of patients with myasthenia gravis who may be at risk of neuromuscular blockade.
Patients taking Doxycycline should be warned that exposure to strong sunlight or ultraviolet light may experience photosensitivity appearing as a severe sunburn reaction. Treatment should cease at the first sign of skin erythema.
In the treatment of venereal disease where co-existent syphilis is suspected, formal diagnostic procedures including dark-field examinations should be employed and monthly serological tests should be conducted for at least four months.
Infections due to Group A beta haemolytic streptococci should be treated for at least 10 days.
Overgrowth of non-susceptible organisms may occur when using antibiotics. Continued observation of the patient is necessary and if a resistant organism appears, antibiotic therapy should be discontinued and appropriate measures instituted.
4.5. Interactions with other medicinal products and other forms of interaction
Patients on anticoagulant therapy may require a reduction in anticoagulant dosage as tetracyclines have been shown to depress plasma prothrombin activity.
Since bacteriostatic drugs may interfere with the bacteriocidal action of penicillin, Doxycycline should not be administered in conjunction with penicillins.
Antacids containing aluminium, calcium, magnesium or zinc, bismuth chelates, sucralfate and iron-containing compounds impair absorption and should therefore not be given to patients taking Doxycycline.
The concurrent use of tetracyclines and methoxyflurane has been reported to result in fatal renal toxicity.
Barbiturates, carbamazepine, primidone and phenytoin have been reported to decrease the half-life of Doxycycline.
A few cases of pregnancy or breakthrough bleeding have been attributed to the concurrent use of tetracycline or oxytetracycline with oral contraceptives.
Doxycycline used concurrently with ciclosporins has been reported to increase the plasma concentration of ciclosporin.
4.6. Fertility, pregnancy and lactation
Use of Doxycycline is contra-indicated during pregnancy as it can have toxic effects on the developing foetus.
Tetracyclines are also found in the milk of lactating women receiving Doxycycline therapy and should therefore not be used in nursing mothers (see contra-indications about tooth development).
4.7. Effects on ability to drive and use machines
Nausea has been reported.
4.8. Undesirable effects
Doxycycline is almost completely absorbed and therefore gastro-intestinal side-effects are infrequent. The following undesirable effects have been observed in patients receiving tetracyclines.
Gastro-intestinal: Nausea, vomiting, anorexia, dysphagia, glossitis, diarrhoea, enterocolitis and inflammatory lesions with monilial overgrowth in the anogenital region. Oesophagitis and oesophageal ulceration have also been reported. A high proportion of these occurrences involved the hydrochloride salt in capsule form and taking medication immediately before going to bed.
Skin: Maculo papular and erythematous rashes. Skin photosensitivity is addressed under “Other Special Warnings and Precautions”. Exfoliative dermatitis has been reported but is uncommon.
Renal: An apparently dose related rise in blood urea has been reported with tetracyclines.
Blood: Thrombocytopenia, neutropenia, haemolytic anaemia and eosinophilia have been reported with tetracyclines.
Hypersensitivity reactions: Exacerbation of systemic lupus erythematosus, anaphylaxis, anaphylactoid purpura, pericarditis, urticaria and angioneurotic oedema.
Other: Bulging fontanelles in infants and benign intracranial hypertension in adults has been reported with the use of tetracyclines. Treatment should cease if evidence of raised intracranial pressure develops. These conditions disappeared rapidly when the drug was discontinued.
Brown-black microscopic discolouration of thyroid tissue has been reported with long-term use of tetracyclines. Thyroid function is normal.
4.9. Overdose
Acute overdosage with antibiotics is rare. In the event of overdosage, gastric lavage and other supportive measures are indicated.
5. PHARMACOLOGICAL PROPERTIES
5.1. Pharmacodynamic properties
Doxycycline is a broad-spectrum antibiotic.
ATC code: J01AA
5.2. Pharmacokinetic properties
Doxycycline hyclate is readily absorbed from the gastro-intestinal tract and absorption is not significantly affected by the presence of food. Following an oral dose of 200mg, the plasma concentration of the drug reaches a level of 2.6mg/ml after 2 hours, falling to 1.45mg/ml at 24 hours. Up to 95% is bound to plasma protein and the half life ranges from 15-25 hours.
Excretion is largely in the faeces as an inactive conjugate or chelate, and approximately 40% may be excreted in the urine.
5.3. Preclinical safety data
Not required.
6. PHARMACEUTICAL PARTICULARS
6.1. List of excipients
Maize starch, magnesium stearate, talc, lactose. Capsule Shell: Green cap: yellow iron oxide (E172), indigotine (E132), titanium dioxide (E171) gelatin. White body: titanium dioxide (E171), gelatin.
6.2. Incompatibilities
Not known.
6.3. Shelf life
3 years: Blister strips composed of 300pm polypropylene, 16mm aluminium foil or blister strips composed of 20pm aluminium foil and 250pm PVC coated with 40gm2 PVdC.
24 months: Blister strips composed of 240pm polypropylene laminated cycloolefin-copolymer (COC) film, laminated both sides with 30pm polypropylene.
6.4. Special precautions for storage
Store in a dry place.
Nature and contents of container
6.5.
Blister strips composed of 300 pm polypropylene or 240pm polypropylene laminated cyclo-olefin-copolymer (COC) film, laminated both sides with 30pm polypropylene, 16 mm aluminium foil or 250pm PVC coated with 40gm2 PVdC, 20pm aluminium foil packed in outer cartons.
6.6. Special precautions for handling (and disposal)
Not applicable.
7. MARKETING AUTHORISATION HOLDER
Sandoz Ltd Woolmer Way,
Bordon,
Hampshire GU35 9QE.
8. MARKETING AUTHORISATION NUMBER
PL: 04416/0264.
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
25 January 1996.
10. DATE OF (PARTIAL) REVISION OF THE TEXT
September 2004.