Doxydox
Hard Gelatin Capsules
Composition :
Each Hard Gelatin Capsule contains:
Doxycycline (as hyclate) 100 mg
Inactive ingredients: Microcrystalline cellulose, maize starch, sodium lauryl sulphate, colloidal silicon dioxide (Aerosil 200), magnesium stearate.
Therapeutic indications :
Doxydox Capsules are used 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 inilueruae, Klebsiella pneumoniae and other organisms. Mycoplasma pneumoniae pneumonia. Treatment of chronic bronchitis. Sinusitis.
– Urinary tract infections: Infections caused by susceptible strains of
Klebsiella species, Enterobacter species, Escherichia coli, Streptococcus {aecalis and other organisms.
– Sexually transmitted diseases: Infections due to Chlamydia trachomalis including uncomplicated urethral, endocervical or rectal infections. Non-gonococcal, urethritis caused by Ureaplasma uteaiyticum. Chancroid I infections due to CalymmaLObacterium granulomatis. Alternative drug in I the treatment of gonorrhoea and syphilis.
– Dermatological infections: Acne vulgaris when antibiotic therapy
is considered necessary. Since doxycycline 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 tetracyclines. such as:
– Ophthalmic infections: Due to susceptible strains of gonococci,
staphylococci and Haemophilus inttueruae. Doxydox capsules are ,
indicated in the treatment of trachoma, although the infectious
agent is not always eliminated, as judged by immunofluorescence.
– Rickettsial infections: Rocky Mountain spotted fever, typhus group, I Q fever and Coxiella endocarditis and tick fevers.
– Miscellaneous: Psittacosis, cholera, melioidosis, leptospirosis, other
infections due to susceptible strains of Yersinia species, Brucella species [m combination with Streptomycin), Clostridium species, Francisella tularensis and chloroquine-resistant falciparum malaria.
– Doxydox capsules are indicated for prophylaxis in the following
conditions: Scrub typhus, travellers’ diarrhoea (enterotoxigenic
Escherichia coli), leptospirosis.
Posology and Method of Administration :
The capsules should be swallowed with plenty of fluid in either the ,
resting or standing position and well before going to bed for the night
to reduce the likelihood of oesophageal irritation and ulceration.
If gastric irritation occurs, it is recommended that Doxydox capsules be given with food or milk.
Adults:
The usual dose of Doxydox Capsules for the treatment of acute
infections in adults is 200 mg on the first day (administered as a 1
single dose or divided into two equal doses with a twelve hour :I
interval), followed by a maintenance dose of 100 mg/day, In the
management of more severe infections (particularly chronic
infections of the urinary tract), 200 mg daily should be given
throughout the treatment period. Exceeding the recommended dosage may result in an increased incidence of side effects.Therapy should be continued at least 24 – 48 hours after symptoms and fever have subsided. When used in streptococcal infections, therapy should be continued for 10 days to prevent the development of rheumatic fever or glomerulonephritis.
Specific infections : Acne vulgaris: 100 mg every other day in the morning with breakfast, for up to 12 weeks.
Sexually transmitted diseases: 100 mg twice daily for 7 days is
recommended in the (ollowing 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 epldidymo-orchitls :caused by Chlamydia trachoma/is or
Neisseria gonorrhoeae: 100 mg twice daily for 10 days.
Primary and secondary syphilis: 300 mg a day in divided doses for at least 10 days.
Louse-borne and tick-borne relapsing fevers: A single dose of 100 mg or 200 mg according to severity.
Chloroquine-resistant falciparum malaria: 200 mg 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 doxycycline; quinine dosage recommendations
vary in different areas.
For the prevention of scrub typhus: 200 mg as a single dose.
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. Data on the use of the drug prophylactically is not
available beyond 21 days.
For the prevention of leptospirosis: 200 mg once each week
throughout the stay in the area and 200 mg at the completion of
the trip. Data on the use of the drug prophylactically are not
available beyond 21 days.
Children: Not recommended.
Elderly: Doxycycline may be prescribed in the usual dose with no
special precautions. No dosage adjustment is necessary in the presence of renal impairment
Renal impairment: Administration of doxycycline at the usual
recommended doses does not lead to excessive accumulation of the
antibiotic in patients with renal impairment. The anti-anabolic action of the tetracyclines may cause an increase in blood urea, but this does not occur with the use of doxycycline ipatients with impaired renal function. Haemodialysis does not alter the serum half-life of doxycycline.
Contraindications :
Hypersensitivity to doxycycline, any of the tetracyclines or any of
the ingredients in the capsules. The use of drugs of the tetracycline class during tooth development (pregnancy, infancy and childhood to the age of 12 years] may cause permanent dtscolouranon of the teeth [yellow-qrey-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 reponed. Doxycycline is contraindicated in these groups of patients.
Children under 12 years of age: Contraindicated in children under the age of 12 years. As with 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 tetracyclines in doses of 25 mg/kg every 6 hours. This reaction was shown to be reverstble when the drug was discontinued. (See above about use during tooth development).
Pregnancy: Doxycycline 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 above about use during tooth development).
Nursing mothers: Tetracylines are excreted into milk and are
therefore contraindicated in nursing mothers. (See above about use
during tooth development).
Special warnings and Precautions for use :
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.
Use in patients with impaired hepatic function: Doxycycline 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 doxycycline.
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 10 rnl/rnin]. 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. The anti-anabolic effect does not occur with the use of doxycycline in patients with impaired renal function.
Microbiological overgrowth: The use of antibiotics may occasionally result in over-growth of non-susceptible organisms, including Candida. If a resistant organism appears, the antibiotic should be discontinued and appropriate therapy instituted.
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 fluid. Bulging fontanelles in infants and benign intracranial hypertension in juveniles and adults have been reported in individuals receiving full therapeutic drugs. These conditions disappeared rapidly when the drug was discontinued.
Porphyria: There have been rare reports of porphyria in patients
receiving tetracyciines.
Venereal disease: When treating venereal diseases, where
coexistent syphilis is suspected, proper diagnostic procedures, including dark-field examinations, should be utilised. In all such cases monthly serological tests should be made for at least four months.
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 gravis.
Systemic lupus erythematous: Tetracyc1ines can cause exacerbation of systemic lupus erythematosus (SLE).
Methoxyflurane: Caution is advised in administering tetracyclines
with methoxyflurane.
Interaction with other medicinal products :
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. Since bacteriostatic drugs may Interfere with the bactericidal action of penicillin, it is advisable to avoid giving doxycycline in conjunction with penicillin.
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 be maximally separated. Phenobarbital, carbamazeplne, primidone and phenytoin may increase the metabolism of doxycycline (reduced half-life]. An
increase in the daily dosage of doxycycline should be considered.
Alcohol may decrease the half-life of doxycycline. The concurrent use of tetracyclines and methoxyflurane has been reported to result in fatal renal toxicity. 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 ciclosporin.
Co-administration should only be undertaken with appropriate
monitoring. Drugs that induce hepatic enzymes such as rifampicin may accelerate the decomposition of doxycycline, thereby decreasing its half-life. Sub-therapeutic doxycycline concentrations may result. Monitoring concurrent use is advised and an increase in
doxycycline dose may be required.
Laboratory test interactions :
False elevations of urinary catecholamine levels may occur due to
interference with the fluorescence test.
Pregnancy and Lactation :
See Contraindications.
Effects on ability to drive and to 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 affect these abilities.
Undesirable effects :
The following adverse reactions have been observed in patients
receiving tetracyclines, including doxycycline.
Hypersensitivity reactions: including anaphylactic shock, anaphylaxis,anaphylactoid reactions. anaphylactoid purpura, hypotension,pericarditis, angioneurotic oedema, exacerbation of systemic lupuserythematosus, dyspnoea, serum sickness, peripheral oedema,tachycardia and urticaria.
Infections and infestations: As with all antibiotics, overgrowth of non-susceptible organisms may cause candidiasis, glossitis,
staphylococcal enterocolitis, pseudomembranous colitis (with
Clostridium di((icile overgrowthl and inflammatory lesions (with
candidal overgrowth) in the anogenital region.
Blood and lymphatic system disorders: Haemolytic anaemia,
thrombocytopenia, neutropenia, porphyria and eosinophilia have
been reported with tetracyclines.
Endocrine disorders: When given over prolonged periods,
tetracyclines have been reported. to produce brown-black microscopicdiscoloration of thyroid tissue. No abnormalities of thyroid functionare known to occur.
Nervous system disorders: Headache. Bulging fontanelles in
infants and benign intracranial hypertension in juveniles and adults
have been reported in some individuals receiving full therapeutic
dosages of tetracycIines. These are reversible on stopping the drug.
Symptoms include blurring of vision, scotomata and diplopia.
Permanent visual loss has been reported.
Ear and labyrinth disorders: Tinnitus.
Gastrointestinal disorders: Gastrointestinal symptoms are usuallymild and seldom necessitate discontinuation of treatment. Abdominalpain, stomatitis, anorexia, nausea, vomiting, diarrhoea, dyspepsia andrarely dysphagia. Oesophagitis and oesophageal ulceration havebeen reported in patients receiving doxycycline. A significantproportion of these cases has occurred with the hydrochloride salt inthe capsule form. Tetracyclines may cause discolouration of teeth andenamel hypoplasia, but usually only after long-term use.
Hepato-biliary disorders: Transient increases in liver function
tests, hepatitis, jaundice, hepatic failure and pancreatitis have been
reported rarely.
Skin and subcutaneous tissue disorders: Rashes including
maculopapular and erythematous rashes occur, exfoliative dermatitis,erythema multiforme, Stevens-Johnson syndrome and toxic epidennal necrolysis. Photosensitivity Musculo-skeletal, connective tissue and bone disorders: Arthralgia and myalgia.
Renal and urinary disorders: Increased blood urea.
Reproductive system and breast disorders: vaginitis.
Overdose :
Acute overdosage with antibiotics is rare. In the event of overdosage,gastric lavage plus appropriate supportive treatment is indicated.Dialysis does not alter serum half-life and thus would not be ofbenefit in treating cases of overdosage.
Pharmacological Properties :
Pharmacodynamic properties:
Doxycycline is primarily a bacteriostatic antibiotic.The main mechanism of action of doxycycline is on proteinsynthesis. Doxycycline passes directly through the lipid bilayer ofthe bacterial cell wall and an energy dependent active transportsystem pumps the drug through the inner cytoplasmic membrane.Once inside the cell, doxycycline inhibits protein synthesis bybinding to 305 ribosomes and prevents the addition of amino acids to the growing peptide chain. Doxycycline will impair protein synthesis in mammalian cells at very high concentrations but these cells lack the active transport system found in bacteria.
Pharmacokinetic properties:
Doxycycline is almost completely absorbed and is not subject to
presystemic metabolism, the mean bioavailability being approximately 93 %. No significant metabolism occurs and Doxycycline is clearedintact by renal and biliary mechanisms. Tissue distribution is good and Doxycycline has a strong affinity for renal and lung tissue. Plasma protein binding is in the range 82-93 % and Doxycycline Is transferred into breast milk. The volume of distribution for doxycycline ranges from 0.9-1.8Ikg-J and the plasma half-life ranges from 18-22 hours.
Special precautions for storage :
Store below 25°C in a dry place.
How supplied :
Doxydox Hard Gelatin Capsules: Carton box containing 1
(AUTransparent PVC) blister of 10 Hard Gelatin capsules and insert
leaflet.
Produced by :
EGYPTIAN INT. PHARMACElTIlCAL INDUSTRIFS co.
E.I. P.I.CO.
10th OF RAMADAN CITY, INDUSTRIAL AREA TENTH, ECYPT
