Doxycycline hyclate 100 mg

Pharmaceutical Group: Antibiotic

Therapeutic indications:Treatment of a variety of infections caused by susceptible strains of Gram-positive and Gram-negative bacteria and certain other micro- organisms

Dosage Form(s): Enteric coated capsule
Pregnancy Category: C

ENTERIDOX 100 contains doxycycline enteric coated pellets. It 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 such as: 

•  Respiratory tract infections like: Pneumonia, Bronchitis, sinusitis
•  Urinary tract infections  
•  Sexually transmitted diseases like:Gonorrhoea and Syphilis and Chlamydia
•  Dermatological infections like: Acne vulgaris
•  Ophthalmic infections
•  Rickettsial infections like: Q fever
•  Other infections like:

Psittacosis, cholera, meliodosis, leptospirosis, other infections due to susceptible strains of Yersinia species, Brucella species (in combination with Streptomycin), Clostridium species, Francisella tularensis and chloroquine-resistant falciparum malaria.

ENTERIDOX 100 Capsules are indicated for prophylaxis in the following conditions: Scrub typhus, travellers diarrhoea (enterotoxigenic Escherichia coli), leptospirosis.

Presentation

 30 Enteric coated capsules 

 Dosage and direction 

Always take The ENTERIDOX 100 capsule exactly as your doctor has prescribed

• The usual dosage of ENTERIDOX 100 for the treatment of acute infections in adults is 200 mg on the first day (as a single dose or in divided doses) followed by a maintenance dose of 100 mg/day.
• In the management of more severe infections (particularily 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 for at least 24 to 48 hours after the 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.

Dosage recommendations in specific infections:

• Acne vulgaris

100mg twice daily with food or fluid for 3 to 6 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: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.

• 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 Doxycycline; quinine dosage recommendations vary in different areas.

• 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.

 Children over 12 years:4mg per Kg of body weight on the first day followed by a maintenance dose of 2mg per Kg of body weight/day 

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 Doxycycline Capsules be given with food. 

Contraindications

• Persons who have shown hypersensitivity to doxycycline, minocycline,tetracycline or any of the excipients. 
• 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

Tetracyclines are excreted into milk and are therefore contraindicated in nursing mothers  

• Children under 12 years of age

Special warnings and precautions

• Patients with impaired hepatic  function should consult a physician before use. 

• Photosensitivity  has been observed in some individuals taking tetracyclines, including doxycycline.  

• 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.
• Clostridium difficile associated diarrhoea (CDAD) has been reported with use of nearly all antibiotics, including doxycycline, and has ranged in severity from mild diarrhoea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C difficile. C difficile produces toxins A and B, which contribute to development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD should be considered in all patients who present with diarrhoea after antibiotic treatment. Careful medical history is necessary since CDAD has been reported to occur over two months after 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

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 was discontinued.

• Porphyria

There have been rare reports of porphyria in patients receiving tetracyclines.

• Venereal disease

When treating venereal disease, where co-existent syphilis is suspected, proper diagnostic procedures, including dark-field examinations, should be utilised. In such cases monthly serological tests should be performed 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 erythematosus

Tetracyclines can cause exacerbation of systemic lupus erythematosus (SLE).

• Methoxyflurane

Caution is advised in administering tetracyclines with methoxyflurane .

• Jarisch-Herxheimer reaction

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.

 Interaction with other medicinal products and other forms of interaction

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 be maximally separated.

-Ergotamine and methysergide

There is an increased risk of ergotism when doxycycline is co-administered with ergotamine and methysergide.

-Methotrexate

Doxycycline increases the risk of methotrexate toxicity; prescribe with caution to patients on methotrexate.

-Kaolin and sucralfate may reduce the absorption of doxycycline.

-Quinapril contains magnesium carbonate and may interfere with the absorption of doxycycline.

Since bacteriostatic drugs may interfere with the bactericidal action of penicillin, it is advisable to avoid giving Doxycycline 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 dosage of concomitant anti-coagulants may be necessary.

-The serum half-life of doxycycline may be shortened when patients are concurrently receiving barbiturates, carbamazepine, primidone or phenytoin. An increase in the daily dosage of Doxycycline 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 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.

-There is a possible increased risk of benign intra-cranial hypertension when doxycycline given with retinoids. Concomitant use should be avoided.

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

-Antibacterials inactivate oral typhoid vaccines. Avoid administration of vaccine during treatment with doxycycline.

Laboratory test interactions

False elevations of urinary catecholamine levels may occur due to interference with the fluorescence test.

Fertility, Pregnancy and lactation
Doxycycline is contraindicated in pregnancy and lactation.

 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 affect these abilities.

 Undesirable effects
The following adverse reactions have been observed in patients receiving tetracyclines, including doxycycline.

• Infections and infestations

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.

• Blood and lymphatic system disorders

Haemolytic anaemia, thrombocytopenia, neutropenia, porphyria, and eosinophilia have been reported with tetracyclines.

• Immune system disorders

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 and urticaria. 

• Endocrine disorders

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. 

• Nervous system disorders

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 diplopia and permanent visual loss has been reported. 

• Ear and labyrinth disorders

Tinnitus

• Gastrointestinal disorders

Gastrointestinal symptoms are usually mild and seldom necessitate discontinuation of treatment. They include abdominal pain, stomatitis, anorexia, nausea, vomiting, diarrhoea, dyspepsia and rarely dysphagia. Oesophagitis and oesophageal ulceration have been reported in patients receiving doxycycline. A significant proportion of these occurred with the hydrochloride salt in the capsule form .

• Tetracyclines may cause discoloration of teeth and enamel hypoplasia, but usually only after long-term use.
• Hepatobiliary disorders

There have been rare reports of hepatotoxicity with transient increases in liver function tests, hepatitis, jaundice, hepatic failure and pancreatitis.

• Skin and subcutaneous tissue disorders

Rashes including maculopapular and erythematous rashes, exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported. Photosensitivity skin reactions  and photo-onycholysis.

• Musculoskeletal and connective tissue disorders
• Arthralgia and myalgia
• Renal and urinary system disorders
• Increased blood urea
• Reproductive system and breast disorders
• Vaginitis

 Overdose
Acute overdosage with antibiotics is rare. In the event of overdosage discontinue medication. Gastric lavage plus appropriate supportive treatment is indicated.

Dialysis does not alter serum half-life and thus would not be of benefit in treating cases of overdosage.