Doxylin 100

/ Dexcel

Adults

The usual dose of Doxycycline hyclate for the treatment of acute infections in adults is 200 mg on the first day (administered as a single dose or divided into two equal doses with a 12 hour 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.

Doxycycline hyclate should be taken with adequate amounts of fluid (at least 100 ml of water). This should be done in the sitting or standing position and the patient should be advised to remain upright for at least thirty minutes after taking a dose. Doxycycline hyclate should be taken well before bedtime to reduce the risk of oesophageal irritation and ulceration. If gastric irritation occurs, it is recommended that Doxycycline hyclate be taken with food or milk. Studies indicate that the absorption of Doxycycline hyclate is not notably influenced by simultaneous ingestion of food or milk.

The tablet must not be divided, chewed or crushed, to prevent irritation to the throat and esophagus.

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 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:

Sexually transmitted diseases: 100 mg twice daily for 7 days is recommended in the following infections: uncomplicated urethral, endocervical or rectal infection caused by Chlamydia trachomatis, non-gonococcal urethritis caused by Ureaplasma urealyticum.

Uncomplicated gonococcal infections (except anorectal infections in men): Doxycycline 100 mg twice daily for 7 days together with intramuscular ceftriaxone.

Acute epididymo-orchitis caused by Chlamydia trachomatis or Neisseria gonorrhea: Doxycycline 100 mg twice daily for 10 days together with intramuscular ceftriaxone.

Primary and secondary syphilis: Non-pregnant penicillin-allergic patients who have primary or secondary syphilis can be treated with the following regimen: doxycycline 100 mg orally twice daily for two weeks, as an alternative to penicillin therapy.

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

Early Lyme Disease (stage 1 and 2): 100 mg twice daily for 10-30 days according to clinical signs, symptoms and response.

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 hyclate; quinine dosage recommendations vary in different areas.

Anthrax due to Bacillus anthracis, including inhalational anthrax (post exposure): 100 mg twice a day for 60 days.

Prophylaxis of Malaria: 100 mg daily in adults. Prophylaxis can begin one or two days before travel to malarial areas. It should be continued daily during travel in the malarial areas and for 4 weeks after the traveler leaves the malarious area.

For the treatment and selective prophylaxis of cholera in adults: 300 mg as a single dose.

For the prevention of scrub typhus: 200 mg as a single dose, once weekly.

For the prevention of travelers’ 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 are not available beyond 21 days.

For the treatment of leptospirosis: 100 mg twice daily for 7 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.

Use in the elderly: Doxycycline hyclate may be prescribed in the usual dose with no special precautions. No dosage adjustment is necessary in the presence of renal impairment.

Use in patients with impaired hepatic function: Doxycycline hyclate should be administered with caution to patients with hepatic impairment or those receiving potentially hepatotoxic drugs.

Use in patients with renal impairment: Studies to date have indicated that administration of Doxycycline hyclate at the usual recommended doses does not lead to accumulation of the antibiotic in patients with renal impairment.

Children

Doxycycline hyclate is contraindicated in children under the age of 12 years. As with other tetracyclines, Doxycycline hyclate 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 reversible when the drug was discontinued.

Doxycycline hyclate 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 microorganisms.

Respiratory tract infections: Pneumonia and other lower respiratory tract infections due to susceptible strains of Streptococcus pneumoniae, Haemophilus influenzae, Klebsiella pneumoniae, Moraxella catarrhalis and other organisms. Mycoplasma pneumonia pneumonia. Treatment of chronic bronchitis, sinusitis.

Urinary tract infections: Infections caused by susceptible strains of Klebsiella species, Enterobacter species, Escherichia coli, Streptococcus faecalis and other organisms.

Sexually transmitted diseases: Infections due to Chlamydia trachomatis including uncomplicated urethral, endocervical or rectal infections. Non-gonococcal urethritis caused by Ureaplasma urealiticum (T-mycoplasma). Doxycycline hyclate 100 is also indicated in infections due to Calymmatobacterium granulomatis. Doxycycline hyclate is an alternative drug in the treatment of gonorrhoea and syphilis.

Since Doxycycline hyclate 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: Treatment of trachoma, although the infectious agent is not always eliminated, as judged by immunofluorescence. Inclusion conjunctivitis may be treated with oral Doxycycline hyclate alone or in combination with topical agents.

Rickettsial infections: Rocky Mountain spotted fever, typhus group, Q fever and Coxiella endocarditis.

Other infections: Psittocosis, brucellosis (in combination with streptomycin), cholera, bubonic plague, louse and tick-borne relapsing fever including stage 1 and stage 2 Lyme disease, leptospirosis, tularaemia glanders, chloroquine-resistant falciparum malaria and acute intestinal amoebiasis (as an adjunct to amoebicides). Infections due to susceptible strains of Bacteroides species and Listeria species.

Doxycycline hyclate is an alternative drug in the treatment of leptospirosis, gas gangrene and tetanus.

Doxycycline hyclate is indicated for prophylaxis in the following conditions: Scrub typhus, traveller’s diarrhoea (enterotoxigenic Escherichia coli), leptospirosis, malaria and cholera.

Anthrax due to Bacillus anthracis, including inhalational anthrax (post exposure): to reduce the incidence or progression of disease following exposure to aerosolized Bacillus anthracis.

Drug interaction: There have been reports of prolonged prothrombin time in patients taking warfarin and Doxycycline. Because the tetracyclines have been shown to depress plasma prothrombin activity, patients who are on anticoagulant therapy may require downward adjustment of their anticoagulant dosage.

Since bacteriostatic drugs may interfere with the bactericidal action of penicillin, it is advisable to avoid giving Doxycycline hyclate in conjunction with penicillin.

The absorption of doxycycline is impaired by concurrently administered antacids containing aluminium, calcium, magnesium or other drugs containing these cations; oral zinc, iron salts or bismuth preparations.

The serum half-life of doxycycline is shortened when patients are concurrently receiving alcohol, barbiturates, carbamazepine, or phenytoin.

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 tetracyclines with oral contraceptives. Concurrent use of tetracycline may render oral contraceptives less effective.

Patients with hypersensitivity to doxycycline, any of its inert ingredients or to any other tetracyclines

Obstructive oesophageal disorders, such as stricture or achalasia.

The use of tetracyclines during tooth development (pregnancy, infancy and childhood to the age of 12 years) may cause permanent discoloration 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.

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 Doxycycline hyclate in patients with impaired renal function.

Use in patients with impaired hepatic function: Doxycycline hyclate 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.

This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

General Severe skin reactions, such as exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported in patients receiving doxycycline. If severe skin reactions occur, doxycycline should be discontinued immediately and appropriate therapy should be instituted.

Photosensitivity: Photosensitivity manifested by an exaggerated sunburn reaction has been observed in some individuals taking tetracyclines, including doxycycline. All patients taking doxycycline should be advised to avoid excessive sunlight or artificial ultraviolet light while receiving 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. Sunscreen or sunblock should be considered.

Microbiological overgrowth: The use of antibiotics may occasionally result in overgrowth of non-susceptible organisms including fungi. Constant observation of the patient is essential. If a resistant organism appears, the antibiotic should be discontinued and appropriate therapy instituted.

General Benign intracranial hypertension (pseudotumor cerebri) has been associated with the use of tetracyclines including doxycycline. Women of childbearing age who are overweight or have a history of IH are at greater risk for developing tetracycline associated IH. Benign intracranial hypertension (pseudotumor cerebri) is usually transient, however cases of permanent visual loss secondary to benign intracranial hypertension (pseudotumor cerebri) have been reported with tetracyclines including doxycycline.

If visual disturbance occurs during treatment, prompt ophthalmologic evaluation is warranted. Since intracranial pressure can remain elevated for weeks after drug cessation patients should be monitored until they stabilize. Concomitant use of isotretinoin and doxycycline should be avoided because isotretinoin is also known to cause benign intracranial hypertension (pseudotumor cerebri).

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 antibacterial agents, including doxycycline, and may range 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.

1. difficile produces toxins A and B which contribute to the 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 must be considered in all patients who present with diarrhoea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

Oesophagitis: cases of oesophageal injuries (oesophagitis and ulceration), sometimes serious, have been reported. Patients should be instructed to take doxycycline capsules with plenty of water (at least 100ml), remain upright and not take their treatment before going to bed. Withdrawal of Doxycycline and investigation of oesophageal disorder should be considered if symptoms such as dyspepsia or retrosternal pain occur. Caution is required in the treatment of patients with known oesophageal reflux disorders.

Veneral disease: When treating venereal disease where co-existent syphilis is suspected, proper diagnostic procedures, including dark-field examinations, should be utilized.  Monthly serological tests should be made for at least 4 months.

Beta-haemolytic streptococci infections: infections due to a group A beta-haemolytic streptococci should be treated for at least 10 days.

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.

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 SLE.

Plasmodium strains: Doxycycline offers substantial but not complete suppression of the asexual blood stages of Plasmodium strains.

Doxycycline does not suppress P. falciparum’s sexual blood stage gametocytes. Subjects completing this prophylactic regimen may still transmit the infection to mosquitoes outside endemic areas.

Common: Hypersensitivity reactions, including anaphylactic shock, anaphylaxis, anaphylactoid reaction, hypotension, pericarditis, angiooedema, exacerbation of systemic lupus erythematosus, dyspnoea, serum sickness, Henoch-Schonlein purpura, peripheral oedema, tachycardia and urticaria, headache, nausea, vomiting, Photosensitivity reaction, rashes including maculopapular and erythematous rashes.

Uncommon: Dyspepsia, (Heartburn/ gastritis)

Rare: Haemolytic anaemia, neutropenia, thrombocytopenia, eosinophilia,  Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), Jarisch- Herxheimer reaction, Brown-black

Microscopic discoloration of thyroid glands, Decreased appetite,  Benign intracranial hypertension (pseudotumor cerebri), fontanelle bulging, Tinnitus, Visual disturbance^d, Flushing, Pancreatitis, pseudomembranous colitis, Clostridium difficile colitis, oesophageal ulcer, oesophagitis, enterocolitis, inflammatory lesions (with monilial overgrowth) in the anogenital region, dysphagia, abdominal pain, diarrhoea, glossitis, Hepatotoxicity, hepatitis, hepatic function abnormal, Toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, dermatitis exfoliative, photoonycholysis, skin hyperpigmentation^c, Arthralgia, myalgia, Blood Urea Increased

Not known: tooth discolouration^e

There have been reports of prolonged prothrombin time in patients taking warfarin and Doxycycline. Because the tetracyclines have been shown to depress plasma prothrombin activity, patients who are on anticoagulant therapy may require downward adjustment of their anticoagulant dosage.

Since bacteriostatic drugs may interfere with the bactericidal action of penicillin, it is advisable to avoid giving Doxycycline hyclate in conjunction with penicillin.

The absorption of doxycycline is impaired by concurrently administered antacids containing aluminium, calcium, magnesium or other drugs containing these cations; oral zinc, iron salts or bismuth preparations.

The serum half-life of doxycycline is shortened when patients are concurrently receiving alcohol, barbiturates, carbamazepine, or phenytoin.

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 tetracyclines with oral contraceptives. Concurrent use of tetracycline may render oral contraceptives less effective.

Pregnancy

Doxycycline hyclate has not been studied in pregnant patients. Doxycycline hyclate should not be used in pregnancy unless, in the judgement of the physician, it is essential for the welfare of the patient.

Results of animal studies indicate that tetracyclines cross the placenta, are found in foetal tissues and can have toxic effects on the developing foetus (often related to retardation of skeletal development). Evidence of embryotoxicity has also been noted in animals treated early in pregnancy.

If any tetracycline is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.

Breastfeeding

Tetracyclines are present in the milk of lactating women who are taking a drug of this kind and should therefore not be used in nursing mothers.

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.

Laboratory Tests

In venereal disease, when co-existent syphilis is suspected, dark field examinations should be done before treatment is started and the blood serology repeated monthly for at least 4 months.

In long-term therapy, periodic laboratory evaluation of organ systems, including hematopoietic, renal, and hepatic studies, should be performed.