Doxydar® 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, Moraxella catarrhalis and other organisms. Mycoplasma pneumoniae. 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 urealyticum (T-mycoplasma). Doxydar® is also indicated in infections due to Calymmatobacterium granulomatis. Doxydar® is an alternative drug in the treatment of gonorrhoea and syphilis.
Since Doxydar® 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:
Doxydar® is indicated in the treatment of trachoma, although the infectious agent is not always eliminated, as judged by immunofluorescence. Inclusion conjunctivitis may be treated with oral Doxydar® alone or in combination with topical agents.
Rickettsial infections:
Rocky Mountain spotted fever, typhus group, Q fever and Coxiella endocarditis.
Other infections:
Psittacosis, 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, Listeria species and Bacillus anthracis.
Doxydar® is an alternative drug in the treatment of leptospirosis, gas gangrene and tetanus.
Doxydar® is indicated for prophylaxis in the following conditions: Scrub typhus, travellers' diarrhoea (enterotoxigenic Escherichia coli), leptospirosis, malaria and cholera.

The usual dose of Doxydar® 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.
Doxydar® capsules should be taken with adequate amounts of fluid (at least 100mls 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. Doxydar® capsules should be taken well before bedtime to reduce the risk of oesophageal irritation and ulceration. If gastric irritation occurs, it is recommended that Doxydar® be given with food or milk. Studies indicate that the absorption of Doxydar® is not notably influenced by simultaneous ingestion of food or milk.
Exceeding the recommended dosage may result in an increased incidence of side effects. Therapy should be continued 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 gonorrhoea
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 Doxydar®; quinine dosage recommendations vary in different areas.

Prophylaxis of malaria
100 mg daily in adults. Prophylaxis can begin 1-2 days before travel to malarious areas. It should be continued daily during travel in the malarious areas and for 4 weeks after the traveller 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 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 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.

Infections due to susceptible strains of Bacillus anthracis
Adults: 100 mg of doxycycline, by mouth, twice a day for 60 days.

Use in the elderly Doxydar® 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 Doxydar® 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 at the usual recommended doses does not lead to accumulation of the antibiotic in patients with renal impairment.

Hypersensitivity to doxycycline, or to any other tetracyclines or to any of the excipients listed in section 6.1. Obstructive oesophageal disorders, such as stricture or achalasia. 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. Doxydar® is therefore contraindicated in these groups of patients. Pregnancy Doxydar® 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. (See above about use during tooth development). Children Doxydar® is contraindicated in children under the age of 12 years. As with other tetracyclines, Doxydar® 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. (See above about use during tooth development).

Use in Patients with Impaired Hepatic Function Doxydar® 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 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 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 over-growth of non-susceptible organisms. Constant observation of the patient is essential. 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.

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.

C. 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 (see section 4.2). 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.

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.

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 for at least four months.

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

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 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.

A few cases of pregnancy or breakthrough bleeding have been attributed to the concurrent use of tetracyclines with oral contraceptives.

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

Laboratory Test Interactions 

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

Pregnancy Category D

Usage in pregnancy  Doxycycline has not been studied in pregnant patients. It should not be used in pregnancy unless, in the judgement of the physician, it is essential for the welfare of the patient. (See Contraindications section about use during tooth development).

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.

Usage in nursing mothers 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 (See Contraindications section about use during tooth development).

The effect of doxycycline on the ability to drive and operate heavy machinery has not been studied. There is no evidence to suggest that doxycycline may affect these abilities.

The following adverse reactions have been observed in patients receiving tetracyclines, including doxycycline.
Adverse Reactions Table

 

System Organ Class	Very Common ≥ 1/10	Common ≥ 1/100 to < 1/10	Uncommon ≥ 1/1000 to < 1/100	Rare ≥ 1/10000 to < 1/1000
Blood and Lymphatic System Disorders				Thrombocytopaenia Haemolytic anaemia Neutropenia Eosinophilia
Immune System Disorders		Anaphylactic Reaction (including Hypersensitivity, Henoch-Schonlein Purpura, hypotension, Pericarditis, Angioedema, Exacerbation of systemic lupus erythematosus, Dyspnoea, Serum sickness, Peripheral oedema, Tachycardia and Urticaria)		Drug Rash with Eosinophilia and Systemic Symptoms (DRESS)
Endocrine Disorders				Brown-black microscopic discoloration of thyroid glands
Metabolism and Nutrition Disorders				Anorexia
Nervous System Disorders		Headache		Fontanelle bulging Benign intracranial hypertension
Ear and Labyrinth Disorders				Tinnitus
Vascular Disorders				Flushing
Gastrointestinal Disorders		Nausea/vomiting	Dyspepsia (Heartburn/gastritis)	Pseudomembranous colitis C.difficile diarrhoea Oesophageal ulcerations Oesophagitis Enterocolitis Inflammatory lesions (with monilial overgrowth) in the anogenital region Abdominal pain Diarrhoea Dysphagia Glossitis
Hepatobiliary Disorders				Hepatotoxicity Hepatitis Hepatic Function Abnormal
Skin and Subcutaneous Tissue Disorders	Photosensitivity Reaction	Rash including maculopapular and erythematous rashes		Toxic Epidermal Necrolysis Stevens-Johnson syndrome Erythema multiforme Exfoliative dermatitis Photoonycholysis
Musculoskeletal, Connective Tissue and Bone Disorders				Arthralgia Myalgia
Renal and Urinary Disorders				Blood Urea Increased

 

CIOMS III categories: Very Common ≥ 1/10 (≥ 10%), Common ≥ 1/100 to < 1/10 (≥ 1% and < 10%), Uncommon ≥ 1/1000 to < 1/100 (≥ 0.1% and < 1%), Rare ≥ 1/10000 to < 1/1000 (≥ 0.01% and < 0.1%).

Fixed Drug Eruptions:
Doxycycline is associated with infrequent cases of fixed drug eruptions. The patient should seek medical help promptly in this situation.

To report any side effects:
Saudi Arabia
• National Pharmacovigilance and Drug Safety Centre (NPC)
• Fax: + 966 112057662
• Call NPC at + 966 112038222, Exts: 2317-2356-2353-2354-2334-2340
• Toll free phone: 8002490000
• E-mail: npc.drug@sfda.gov.sa
• Website: www.sfda.gov.sa/npc

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.

Pharmacotherapeutic group: Tetracyclines, ATC Code: J01 AA02.
Doxydar® is primarily bacteriostatic and is believed to exert its antimicrobial effect by the inhibition of protein synthesis. Doxydar® is active against a wide range of Gram-positive and Gram-negative bacteria and certain other micro-organisms.
Doxydar® has a high degree of lipid solubility and a low affinity for calcium. It is highly stable in normal human serum. Doxydar® will not degrade into an epianhydro form.

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 200 mg 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.
Studies have shown no significant difference in serum half-life of Doxycycline (range 18 to 22 hours) in individuals with normal or severely impaired renal function.
Haemodialysis does not alter the serum half-life of Doxycycline.

Not applicable.

Sodium laurilsulfate, magnesieum stearate, starch.

None known

48 Months

Protect from light. Store in a dry place. Do not store above 30ºC.

Immediate packaging	Outer packaging
PVC film Aluminum foil	Cardboard box and insert

Doxydar® capsules are available in aluminum packs that contain of 6, 8 or 10 capsules (one strip contains 6, 8 or 10 capsules), 500 capsules (50 strips, each strip contains 10 capsules).
Not all pack sizes may be marketed

No special requirements