DOXYLAR* CAPSULES 100 MG, RAMYSIS CAPSULES 100 MG, DOXYCYCLINE CAPSULES BP 100 MG - summary of medicine characteristics

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.

Capsule

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.

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, non-gonoccal 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 micro-organisms 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.

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

Consideration should be given to official guidance on the appropriate use of antibacterial agents.

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 aged 12 years to less than 18 years

The usual dosage of Doxycycline capsules in for the treatment of acute infections in adults and children aged 12 years to less than 18 years is 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.

Children aged 8 years to less than 12 years. (Section 4.4)

The use of doxycycline for the treatment of acute infections in children aged 8 years to less than 12 years should be carefully justified in situations where other drugs are not available, are not likely to be effective or are contraindicated.

In such circumstance, the doses for the treatment of acute infections are: For children 45 kg or less- Initial dose: 4.4 mg/kg (in single or 2 divided doses) with maintenance dose: 2.2 mg/kg (in single or 2 divided doses). In the management of more severe infections, up to 4.4 mg/kg should be given throughout treatment.

For children, over 45 kg – Dose administered for adults should be used.

Children aged from birth to less than 8 years.

Doxycycline should not be used in children aged younger than 8 years due to the risk of teeth discolouration. (Section 4.4 and 4.8)

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.

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.

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).

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.

Method of administration: oral.

4.3 Contraindications

Doxycycline should not be administered to patients who have shown hypersensitivity to tetracyclines or to any of the excipients listed in section 6.1.

Pregnancy: Doxycycline capsules is contraindicated in pregnancy. It appears that the risks associated with the use of tetracyclines during pregnancy are predominantly due to effects on teeth and skeletal development. (See Section 4.4 above about regarding use during tooth development).

Nursing mothers: Tetracyclines are excreted into milk and are therefore contraindicated in nursing mothers. (See Section 4.4 above about regarding use during tooth development).

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).

Some patients with spirochete infections may experience a Jarisch-Herxheimer reaction shortly after doxycycline treatment is started. Patients should be reassured that this is a usually self-limiting consequence of antibiotic treatment of spirochete infections.

The use of drugs of the tetracycline class during tooth development (last half of pregnancy; infancy and childhood to the age of 8 years) may cause permanent discolouration of the teeth (yellow-greybrown).

This adverse reaction is more common during long-term use of the drugs but has been

observed following repeated short-term courses. Enamel hypoplasia has also been reported. Use doxycycline in paediatric patients aged younger than 8 years only when the potential benefits are expected to outweigh the risks in severe or life-threatening conditions (e.g. Rocky Mountain spotted fever), only when there are no adequate alternative therapies.

Although the risk of permanent teeth staining is rare in children aged 8 years to less than 12 years, the use of doxycycline should be carefully justified in situations where other drugs are not available, are not likely to be effective or are contraindicated.

4.5 Interaction 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.

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. Tooth discolouration (reversible and superficial discolouration of permanent teeth has been reported with the use of doxycycline but frequency cannot be estimated from available data).

Skin: The most commonly reported reaction is photosensivity. Maculo-papular 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.

Anxiety and photoonycholysis have also been reported (frequency: rare).

Immune system disorders: Frequency ‘Not known’: Jarisch-Herxheimer reaction (see section 4.4)

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.

5.1 Pharmacodynamic properties

Doxycycline is a broad-spectrum antibiotic.

ATC code: J01AA

5.2 Pharmacokinetic properties

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

Cmax = 3.04|lg/ml

Tmax = 3 hours.

5.3 Preclinical safety data

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 I6um aluminium foil, 3C)C)Lim transparent polypropylene or blister strips composed of 20um aluminium foil and 250^m PVC coated with 40gm2 PVdC.

24 months: Blister strips composed of 240^m polypropylene laminated cyclo-olefin-copolymer (COC) film, laminated both sides with 30^m 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, 300um transparent polypropylene or 240um polypropylene laminated cyclo-olefin-coploymer (COC) film, laminated both sides with 30 um polypropylene or 20um aluminium foil and 25C)Lim PVC coated with 40gm2PVdC.

Blister strips packed into cartons.

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

6.6 Special precautions for disposal

Not applicable.

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