Summary of product characteristics

SUMMARY OF PRODUCT CHARACTERISTICS
DOXAT 100
1. Trade Name of the medical product
2. Qualitative and quantitative composition
Doxycycline hydrochloride equivalent to Doxycycline 100mg, Microcrystalline cellulose 245mg, Lactose 174mg, Sodium starch glycolate 48mg, Povidone 3mg, Polyethylene glycol 6000 6mg, Colloidal silicon dioxide 3mg, Yellow film coating suspension per gram: Hydroxypropylmethylcellulose 2910 11.3mg, Polyethylene glycol 400 1.4mg, Titanium dioxide 1.4mg, Riboflavine 3. Pharmaceutical form
4. Clinical information
4.1 Therapeutic Indications
DOXAT has been found clinically effective in the treatment of a variety of infections caused by susceptible strains of Gram-positive and Gram-negative bacteria and certain other micro-organisms. Respiratory tract infections Pneumonia and other lower respiratory tract
infections due to susceptible strains of Streptococcus pneumoniae, Haemophilus influenzae, Klebsiella pneumoniae and other organisms. Mycoplasma pneumoniae pneumonia. Treatment of chronic bronchitis, Urinary tract infections caused by susceptible strains of Klebsiella species,
Enterobacter species, Escherichia coli, Streptococcus faecalis and other Sexually transmitted diseases Infections due to Chlamydia trachomatis
including uncomplicated urethral, endocervical or rectal infections. Non- gonococcal urethritis caused by Ureaplasma urealyticum (T-mycoplasma). DOXAT is also indicated in chancroid, granuloma inguinale and lymphogranuloma venereum. DOXAT is an alternative drug in the treatment of Skin infections Acne vulgaris, when antibiotic therapy is considered
Since DOXAT is a member of the tetracycline series of antibiotics, it may be expected to be useful in the treatment of infections which respond to other Ophthalmic infections Due to susceptible strains of gonococci,
staphylococci and Haemophilus influenzae. Trachoma, although the infectious agent, as judged by immunofluorescence, is not always eliminated. Inclusion conjunctivitis may be treated with oral DOXAT alone or in combination with Rickettsial infections Rocky Mountain spotted fever, typhus group, Q fever,
Other infections Psittacosis, brucellosis (in combination with streptomycin),
cholera, bubonic plague, louse and tick-borne relapsing fever, tularaemia glanders, melioidosis, chloroquine-resistant falciparum malaria and acute intestinal amoebiasis (as an adjunct to amoebicides). DOXAT is an alternative drug in the treatment of leptospirosis, gas gangrene DOXAT is indicated for prophylaxis in the following conditions: Scrub typhus, travellers' diarrhoea (enterotoxigenic Escherichia coli), leptospirosis and malaria. Prophylaxis of malaria should be used in accordance to current guidelines, as resistance is an ever changing problem. 4.2 Posology and method of administration
Adults
The usual dosage of DOXAT for the treatment of acute infections in adults is 200mg on the first day (as a single dose or in divided doses) followed by a maintenance dose of 100mg/day. In the management of more severe infections, 200mg daily should be given throughout treatment. Dispersible Tablets are for oral administration only. DOXAT-D tablets are administered by drinking a suspension of the tablets in This should be done in the sitting or standing position and well before retiring at night to reduce the risk of oesophageal irritation and ulceration. If gastric irritation occurs, it is recommended that DOXAT be given with food or milk. Studies indicate that the absorption of DOXAT is not notably influenced by Exceeding the recommended dosage may result in an increased incidence of side effects. Therapy should be continued for at least 24 to 48 hours after When used in streptococcal infections, therapy should be continued for 10 days to prevent the development of rheumatic fever or glomerulonephritis. Dosage recommendations in specific infections:
Acne vulgaris 50mg daily with food or fluid for 6 to 12 weeks.
Sexually transmitted diseases 100mg twice daily for 7 days is
recommended in the following infections: uncomplicated gonococcal infections (except anorectal infections in men); uncomplicated urethral, endocervical or rectal infection caused by Chlamydia trachomatis; non- gonococcal urethritis caused by Ureaplasma urealyticum. Acute epididymo- orchitis caused by Chlamydia trachomatis or Neisseria gonorrhoea 100mg twice daily for 10 days. Primary and secondary syphilis: Non-pregnant penicillin-allergic patients who have primary or secondary syphilis can be treated with the following regimen: doxycycline 200mg orally twice daily for two weeks, as an alternative to penicillin therapy. Louse and tick-borne relapsing fevers A single dose of 100 or 200mg
Treatment of chloroquine-resistant falciparum malaria 200mg daily for at
least 7 days. Due to the potential severity of the infection, a rapid-acting schizonticide such as quinine should always be given in conjunction with DOXAT; quinine dosage recommendations vary in different areas. Prophylaxis of malaria 100mg daily in adults and children over the age of 12
years. Prophylaxis can begin 1-2 days before travel to malarial areas. It should be continued daily during travel in the malarial areas and for 4 weeks after the traveller leaves the malarial area. For current advice on geographical resistance patterns and appropriate chemoprophylaxis, current guidelines or the Malaria Reference Laboratory should be consulted, details of which can be found in the British National Formulary (BNF). For the prevention of scrub typhus 200mg as a single dose.
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. Data on the use of the drug prophylactically are not available beyond 21 days. For the prevention of leptospirosis 200mg once each week throughout the
stay in the area and 200mg at the completion of the trip. Data on the use of the drug prophylactically are not available beyond 21 days. Use for children See under “Contra-indications”.
Use in the elderly DOXAT may be prescribed in the elderly in the usual
dosages with no special precautions. No dosage adjustment is necessary in the presence of renal impairment. The DOXAT-D dispersible tablet may be preferred for the elderly since it is less likely to be associated with Use in patients with impaired hepatic function See under “Special
Use in patients with renal impairment Studies to date have indicated that
administration of DOXAT at the usual recommended doses does not lead to accumulation of the antibiotic in patients with renal impairment see under “Special warnings and precautions for use”. 4.3 Contraindications
Persons who have shown hypersensitivity to doxycycline, any of its inert ingredients or to any of the tetracyclines. The use of drugs of the tetracycline class during tooth development (pregnancy, infancy and childhood to the age of 12 years) may cause permanent discolouration of the teeth (yellow-grey-brown). 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. DOXAT is therefore contra-indicated in these groups of Pregnancy DOXAT is contra-indicated 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 above about use Nursing mothers Tetracyclines are excreted into milk and are therefore
contra-indicated in nursing mothers. (See above about use during tooth Children DOXAT is contra-indicated in children under the age of 12 years. As
with other tetracyclines, DOXAT forms a stable calcium complex in any bone- forming tissue. A decrease in the fibula growth rate has been observed in prematures given oral tetracyclines in doses of 25mg/kg every 6 hours. This reaction was shown to be reversible when the drug was discontinued. (See above about use during tooth development). 4.4 Special warnings and precautions for use
Use in patients with impaired hepatic function DOXAT should be
administered with caution to patients with hepatic impairment or those receiving potentially hepatotoxic drugs. Abnormal hepatic function has been reported rarely and has been caused by both the oral and parenteral administration of tetracyclines, including Use in patients with renal impairment Excretion of doxycycline by the
kidney is about 40%/72 hours in individuals with normal renal function. This percentage excretion may fall to a range as low as 1-5%/72 hours in individuals with severe renal insufficiency (creatinine clearance below 10ml/min). Studies have shown no significant difference in the serum half-life of doxycycline in individuals with normal and severely impaired renal function. Haemodialysis does not alter the serum half-life of doxycycline. The anti- anabolic action of the tetracyclines may cause an increase in blood urea. Studies to date indicate that this anti-anabolic effect does not occur with the use of DOXAT in patients with impaired renal function. Photosensitivity Photosensitivity manifested by an exaggerated sunburn
reaction has been observed in some individuals taking tetracyclines, including doxycycline. Patients likely to be exposed to direct sunlight or ultraviolet light should be advised that this reaction can occur with tetracycline drugs and treatment should be discontinued at the first evidence of skin erythema. Microbiological overgrowth The use of antibiotics may occasionally result in
the overgrowth of non-susceptible organisms including Candida. If a resistant organism appears, the antibiotic should be discontinued and appropriate Pseudomembranous colitis has been reported with nearly all antibacterial agents, including doxycycline, and has ranged in severity from mild to life- threatening. It is important to consider this diagnosis in patients who present with diarrhoea subsequent to the administration of antibacterial agents. Oesophagitis Instances of oesophagitis and oesophageal ulcerations have
been reported in patients receiving capsule and tablet forms of drugs in the tetracycline class, including doxycycline. Most of these patients took medications immediately before going to bed or with inadequate amounts of Bulging fontanelles in infants and benign intracranial hypertension in
juveniles and adults have been reported in individuals receiving full therapeutic dosages. These conditions disappeared rapidly when the drug Porphyria There have been rare reports of porphyria in patients receiving
Venereal disease When treating venereal disease, where co-existent syphilis
is suspected, proper diagnostic procedures including dark-field examinations should be utilised. In all such cases monthly serological tests should be made Beta-haemolytic streptococci infections Infections due to group A beta-
haemolytic streptococci should be treated for at least 10 days. Myasthenia gravis Due to a potential for weak neuromuscular blockade, care
should be taken in administering tetracyclines to patients with myasthenia Systemic lupus erythematosus Tetracyclines can cause exacerbation of
Methoxyflurane Caution is advised in administering tetracyclines with
4.5 Interactions with other medications and other forms of
interactions
The absorption of doxycycline may be impaired by concurrently administered antacids containing aluminium, calcium, magnesium or other drugs containing these cations; oral zinc, iron salts or bismuth preparations. Dosages should Since bacteriostatic drugs may interfere with the bactericidal action of penicillin, it is advisable to avoid giving DOXAT in conjunction with penicillin. There have been reports of prolonged prothrombin time in patients taking warfarin and doxycycline. Tetracyclines depress plasma prothrombin activity and reduced doses of concomitant anticoagulants may be necessary. The serum half-life of doxycycline may be shortened when patients are concurrently receiving barbiturates, carbamazepine or phenytoin. An increase in the daily dosage of DOXAT should be considered. Alcohol may decrease the half-life of doxycycline. A few cases of pregnancy or breakthrough bleeding have been attributed to the concurrent use of tetracycline antibiotics with oral contraceptives. Doxycycline may increase the plasma concentration of cyclosporin. Co- administration should only be undertaken with appropriate monitoring. The concurrent use of tetracyclines and methoxyflurane has been reported to result in fatal renal toxicity. See section 4.4 Laboratory test interactions
False elevations of urinary catecholamine levels may occur due to interference with the fluorescence test. 4.6 Pregnancy and lactation
4.7 Effects on ability to drive and use machines
The effect of doxycycline on the ability to drive or operate heavy machinery has not been studied. There is no evidence to suggest that doxycycline may 4.8 Undesirable effects
The following adverse reactions have been observed in patients receiving Autonomic nervous system Flushing.
Body as a whole Hypersensitivity reactions, including anaphylactic shock,
anaphylaxis, anaphylactoid reaction, anaphylactoid purpura, hypotension, pericarditis, angioneurotic oedema, exacerbation of systemic lupus erythematosus, dyspnoea, serum sickness, peripheral oedema, tachycardia Central and Peripheral nervous system Headache. Bulging fontanelles in
infants and benign intracranial hypertension in juveniles and adults have been reported in individuals receiving full therapeutic dosages of tetracyclines. In relation to benign intracranial hypertension, symptoms included blurring of vision, scotomata and diplopia. Permanent visual loss has been reported. Gastro-intestinal Gastro-intestinal symptoms are usually mild and seldom
necessitate discontinuation of treatment. Abdominal pain, anorexia, nausea, vomiting, diarrhoea, dyspepsia and rarely dysphagia. Oesophagitis and oesophageal ulceration have been reported in patients receiving DOXAT. A significant proportion of these occurred with the hyclate salt in the capsule form. (See 'Special warnings and precautions for use' section). Hearing/Vestibular Tinnitus.
Haemopoietic
porphyria, and eosinophilia have been reported with tetracyclines. Liver/Biliary Transient increases in liver function tests, hepatitis, jaundice,
hepatic failure and pancreatitis have been reported rarely. Musculo-Skeletal Arthralgia and myalgia.
Skin Rashes including maculopapular and erythematous rashes, exfoliative
dermatitis, erythema multiforme, Steven-Johnson syndrome and toxic epidermal necrolysis. Photosensitivity skin reactions (see 'Special warnings Superinfection As with all antibiotics, overgrowth of non-susceptible
organisms may cause candidiasis, glossitis, staphylococcal enterocolitis, pseudomembranous colitis (with Clostridium difficile overgrowth) and inflammatory lesions (with candidal overgrowth) in the anogenital region. Similarly there have been reports for products in the tetracycline class of Urinary system Increased blood urea. (See 'Special warnings and
Other When given over prolonged periods, tetracyclines have been reported
to produce brown-black microscopic discolouration of thyroid tissue. No abnormalities of thyroid function are known to occur. Tetracyclines may cause discoloration of teeth and enamel hypoplasia, but 4.9 Overdose
Acute overdosage with antibiotics is rare. In the event of overdosage, gastric lavage and other supportive measures are indicated. Dialysis does not alter serum half-life and thus would not be of benefit in treating 5. Pharmacological properties
5.1 Pharmacodynamic properties
DOXAT is primarily bacteriostatic and is believed to exert its antimicrobial effect by the inhibition of protein synthesis. DOXAT is active against a wide range of Gram-positive and Gram-negative bacteria and certain other micro- 5.2 Pharmacokinetic properties
Tetracyclines are readily absorbed and are bound to plasma proteins in varying degrees. They are concentrated by the liver in the bile and excreted in the urine and faeces at high concentrations and in a biologically active form. Doxycycline is virtually completely absorbed after oral administration. Studies reported to date indicate that the absorption of doxycycline, unlike certain other tetracyclines, is not notably influenced by the ingestion of food or milk. Following a 200mg dose, normal adult volunteers averaged peak serum levels of 2.6 micrograms/ml of doxycycline at 2 hours decreasing to 1.45 micrograms/ml at 24 hours. Doxycycline has a high degree of lipid solubility and a low affinity for calcium. It is highly stable in normal human serum. Doxycycline will not degrade into an epianhydro form. 6. Pharmaceutical information
6.1 List of excipients
Microcrystalline cellulose, Lactose, Sodium starch glycolate, Povidone, Polyethylene glycol 6000, Colloidal silicon dioxide, Magnesium stearate. Hydroxypropylmethylcellulos 2910, Polyethylene glycol 400, Titanium dioxide 6.2 Incompatibilities
6.3 Shelf-life
6.4 Special precautions for storage
Store in a dry place protected from light, below 25ºC. 6.5 Nature and contents of container
6.6 Instructions for use/handling
7. Marketing authorization holder
Aegis Ltd, Ergates Ind. Area P.O. Box 28629, 2081 Nicosia, CYPRUS, 8. Marketing authorization number
9. Date of first authorization/renewal of authorization
10. Date of partial revision of the text

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