SUMMARY OF PRODUCT CHARACTERISTICS

1. NAME OF MEDICINAL PRODUCT

Doxylar* Capsules 100mg Ramysis Capsules 100mg Doxycycline Capsules BP 100mg.

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each 100mg capsule contains doxycycline hydrochloride equivalent to doxycycline BP 100mg.

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Capsule

4. CLINICAL PARTICULARS

4.1. Therapeutic Indications

Treatment

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.

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 urelyticulum (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.

Miscellaneous: psittacosis, leptospirosis, cholera, melioidosis, other infections due to susceptible strains of Yersinia species, Brucella species (in combination with streptomycin), Clostridium species, Francisella tularensis and chloroquinine-resistant falciparum malaria.

Prophylaxis: Doxycycline is also indicated in the prophylactic treatment of leptospirosis, scrub typhus and 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.

4.2. Posology and Method of Administration

An adequate volume of fluid should be taken when administering doxycycline capsules; this should preferably be taken by the patient whilst in an upright position and not immediately before going to bed.

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.

Recommended doses:

Adults and children over 12 years of age:

200mg on the first day (administered as a single dose or divided into 2 equal doses with a 12 hour interval) followed by a maintenance dose of 100mg/day. For more severe infections (particularly chronic infections of the urinary tract) 200mg should be given throughout the treatment.

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.

Children:

Doxycycline Capsules must not be given to children under 12 years of age. Specific infections:

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, 100mg should be taken twice daily for 7 days.

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 4 months.

For the treatment of acute epididymo-orchitis caused by Chlamydia trachomatis or Neisseria gonorrhoeae; 100mg twice daily for 10 days.

For the treatment of primary and secondary syphilis: 300mg a day in divided doses for at least 10 days.

Louse and tick-borne relapsing fevers: A single dose of 100mg or 200mg according to severity.

Chloroquine-resistant falciparum malaria: 200mg 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: 200mg on the first day of travel (administered as a single dose or as 100mg every 12 hours), followed by 100mg daily throughout the stay in the area.

For the prevention of scrub typhus: 200mg to be taken as a single dose.

For the prevention of leptospirosis: 200mg to be taken once a week throughout the stay in the area and 200mg 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 Formulary (BNF).

4.3. Contra-indications

Doxycycline should not be administered to patients who have shown hypersensitivity to tetracyclines. Doxycycline is contra-indicated in pregnancy, lactation and children under 12 years of age.

4.4. Special Warnings and Precautions for Use

Doxycycline possibly increases the plasma concentration of cyclosporin. Combined administration should be undertaken only with appropriate monitoring.

The antiepileptic drugs carbamazepine, phenobarbitone, phenytoin and primidone increase the metabolism of doxycycline.

Diuretics may aggravate nephrotoxicity by volume depletion.

Doxycycline should be administered with caution to patients with hepatic impairment, porphyria or those receiving other potentially hepatotoxic drugs.

Doxycycline can cause weak neuromuscular blockade - use with caution in myasthenia gravis.

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 discomfort.

Tetracycline therapy may cause exacerbation of systemic lupus erythematosus (SLE).

4.5. Interactions with other medicinal products and other forms of interaction

An increase in anticoagulant effect may occur with concomitant use of tetracyclines.

Since bacteriostatic drugs may interfere with the bacteriocidal action of penicillin, doxycycline should not be administered in conjunction with penicillins.

Tetracyclines bind to di-/tri-valent cations. Absorption from the gastrointestinal tract is impaired by the concomitant administration of iron, calcium, aluminium,

magnesium, bismuth and zinc salts (interactions occur with specified salts, antacids, bismuth containing ulcer-healing drugs, and quinapril which contains a magnesium carbonate excipient). Dosages should be maximally separated.

Absorption of tetracyclines is impaired by food, milk and milk products.

The concurrent use of tetracyclines and methoxyflurane has been reported to result in fatal renal toxicity.

The concomitant use of tetracycline may reduce the efficacy of oral contraceptives.

See also 4.4 Special warnings and precautions for use.

4.6. Fertility, pregnancy and lactation

Doxycycline is contra-indicated during pregnancy and lactation.

Tetracyclines taken during pregnancy may affect foetal skeletal development and cause permanent discolouration and malformation of teeth.

4.7. Effects on Ability to Drive and Use Machines

No known effects on ability to drive and use machines have 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 and diarrhoea. Oesophagitis and oesophageal ulceration have also been reported, usually when taken before bed or with inadequate fluids. A few cases of pancreatitis have been reported.

Skin: The most commonly reported reaction is photosensitivity. Maculopapular and erythematous rashes, pruritus, bullous dermatoses, and exfoliative dermatitis may occur.

Hepatic: Transient increases in liver function tests, hepatitis, jaundice and hepatic failure have been reported rarely.

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: anaphylaxis, anaphylactoid purpura, pericarditis, urticarial rash and angioneurotic oedema.

Other: Bulging fontanelles in infants and benign intracranial hypertension in juveniles and adults has been reported. Presenting features were headache and visual disturbances including blurring of vision, scotomata and diplopia. Permanent visual loss has been reported. Treatment should cease if evidence of raised intracranial pressure develops.

Teeth discolouration may occur, becoming obvious after repeated doses.

Brown-black microscopic discolouration of thyroid tissue has been reported with long-term use of tetracyclines. Thyroid function is normal.

As with all antibiotics overgrowth of non-susceptible organisms may cause candidiasis, pseudomembranous colitis (Clostridium difficile overgrowth), glossitis, stomatitis, vaginitis, or staphylococcal enterocolitis.

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

The following results were obtained with Doxycycline Capsules (2 x 100mg) in adult healthy volunteers:

Cmax = 3.04pg/ml Tmax = 3 hours.

5.3. Preclinical Safety Data

Not required.

6. PHARMACEUTICAL PARTICULARS

6.1.    List of Excipients

Maize starch, magnesium stearate, talc, lactose, indigotine (E132), titanium dioxide (E171), yellow iron oxide (E172) and gelatin.

6.2.    Incompatibilities

Not known.

6.3.    Shelf Life

36 months: Securitainers or blister strips composed of 16pm aluminium foil, 300pm transparent polypropylene 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 cool dry place. Protect from light.

6.5.    Nature and Contents of Container

Securitainers or blister strips composed of 16mm aluminium foil, 300pm transparent polypropylene or 240pm polypropylene laminated cyclo-olefin-coploymer (COC) film, laminated both sides with 30pm polypropylene or 20pm aluminium foil and 250pm PVC coated with 40gm² PVdC.

Blister strips packed into cartons.

Pack sizes: 8, 10, 14, 20, 21, 28, 30, 50 or 56.

6.6. Special precautions for disposal/handling

Not applicable.

7.    MARKETING AUTHORISATION HOLDER

Sandoz Ltd Woolmer Way Bordon

Hampshire GU35 9QE

8.    MARKETING AUTHORISATION NUMBER(S)

PL 4416/0007

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

16/12/2008

10    DATE OF REVISION OF THE TEXT

16/12/2008