Codo

Uses

Doxycycline has a very wide spectrum of activities and has been used in the treatment of a large number of infections caused by susceptible organisms.

Respiratory tract infections: Pneumonia, influenza, pharyngitis, tonsillitis, bronchitis, sinusitis, otitis media and other streptococcal and staphylococcal infections where tetracycline resistance is not a problem.

Genitourinary tract infections: Pyelonephritis, cystitis, urethritis, gonorrhea, epididymitis, syphilis, chancroid and granuloma inguinale.

Chlamydia: Lymphogranuloma venereum, psittacosis, trachoma.

Intestinal diseases: Whipples disease, tropical sprue, blind loop syndrome.

In acute intestinal amoebiasis: Doxycycline may be a useful adjunct to amoebicides.

Bacillary infections: Brucellosis, tularemia, cholera, travelers diarrhea

Acne: Acne vulgaris, acne conglobata and other forms of acne.

Other infections: Actinomycosis, yaws, relapsing fever, leptospirosis, typhus, rickettsial pox and Q fever, Cellulitis furunculosis, abscess and infections caused by Mycobacterium marinum, Bordetella pertussis and Bacillus anthracis.

Codo is also used to associated treatment for these conditions: Acinetobacter infection, Acne Rosacea, Actinomycosis, Acute epididymo-orchitis caused by Chlamydia Trachomatis, Anal chlamydia infection, Bacterial Infection caused by Enterobacter aerogenes, Bartonellosis, Brucellosis, Campylobacter Infection, Chancroid, Chlamydial Urethritis, Chlamydial cervicitis, Cholera, Clostridium Infections, Epididymo-orchitis gonococcal, Gonorrhea, Granuloma Inguinale, Infection Due to Escherichia Coli, Intestinal Amebiasis, Listeria infection, Lymphogranuloma Venereum, Necrotizing ulcerative gingivostomatitis, Plague, Plasmodium Infections, Primary Syphilis, Psittacosis, Q Fever, Rectal infection, Rectal infection caused by Chlamydia Trachomatis, Recurring fever caused by Borrelia recurrentis, Relapsing fever caused by Borrelia recurrentis, Respiratory Tract Infections (RTI), Rickettsialpox, Rocky Mountain Spotted Fever, Secondary Syphilis, Severe Acne, Shigella Infection, Skin Infections, Tick-borne fever, Trachoma, Trachoma inclusion conjunctivitis, Tularemia, Typhus Fever, Upper Respiratory Tract Infection, Ureaplasma urethritis, Urinary Tract Infection, Yaws, Inhaled anthrax caused by Bacillus anthracis

How Codo works

In bacterial replication, an interaction that is important for translation initiation of proteins occurs at the 3′ end of the 16S rRNA, found on the ribosome on the 30S subunit , , . The 30S subunit is the smaller subunit of the ribosome of prokaryotes, including bacteria.

Tetracyclines such as doxycycline are thought to inhibit translation by binding to the 16S rRNA portion of the ribosome , preventing binding of tRNA to the RNA-30S bacterial ribosomal subunit, which is necessary for the delivery of amino acids for protein synthesis. As a result of the above actions, the initiation of protein synthesis by polyribosome formation is blocked. This stops the replication of bacteria and produces a bacteriostatic effect .

Dosage

Codo dosage

Oral-

Susceptible infections:

• 200 mg on day 1 as a single or in divided doses, followed by 100 mg once daily. Severe infections: Maintain initial dose throughout the course of treatment.

Relapsing fever and louse-borne typhus:

• 100 or 200 mg as a single dose.

Prophylaxis of scrub typhus:

• 200 mg as a single dose.

Uncomplicated gonorrhoea:

• 100 mg bid for 7 days or a single dose of 300 mg followed by a 2nd similar dose 1 hr later.

Syphilis:

• 100-200 mg bid for at least 14 days.

Acne:

• 50 mg daily for 6-12 wk.

Chloroquine resistant falciparum malaria acute attack:

• 200 mg daily for at least 7 days, w/ or after treatment w/ quinine.

Treatment and postexposure prophylaxis of inhalation anthrax:

• 100 mg bid, to complete a 60-day course after treatment w/ 1-2 other antibacterials.

Prophylaxis of chloroquine-resistant malaria:

• 100 mg daily for up to 2 yr.

Topical/Cutaneous-

Periodontitis:

• As 10% controlled-release subgingival preparation: Inject the contents of the syringe into the periodontal pocket, may be repeated 4 mth after initial treatment.

Intravenous-

Susceptible infections: 200 mg on day 1 followed by 100-200 mg daily depending on the severity of infection.

Side Effects

Gastrointestinal disterbances,eg. anorexia, vomiting, dysentry etc. overgrowth of resistant organisms may cause Glossitis, Stomatitis, or Staphylococcal enterocolitis; Apart from these skin rashes, purpura may occur. Photosensitivity and dermatological reactions are rare.

Toxicity

There are various precautions to be undertaken while doxycyline is administered . A full list of adverse events is included in the "Adverse Effects" section of this drug entry.

A note on tooth development and tetracycline use

The use of tetracyclines, including doxycycline, during tooth development (i.e. the last half of pregnancy, throughout infancy, and in childhood up to 8 years of age) may lead to tooth enamel hypoplasia and yellow-gray discoloration of teeth. It is advisable not to administer doxycycline in this age group according to the FDA label, except for in cases of post-exposure cases of anthrax (including inhalational anthrax) . Other sources state that doxycycline should not be administered in children under 12 years .

A note on Clostridium difficile Clostridium difficile associated diarrhea (CDAD) and antibiotic associated pseudomembranous colitis may result from doxycycline use. Administering antibacterial agents changes the normal flora of the colon leading to an overgrowth of C. difficile. This bacteria produces toxins A and B, which contribute to the development of CDAD . in moderate to severe cases, therapy with a suitable oral antibacterial agent effective against Clostridium difficile should be considered. Fluids, electrolytes and protein replacement should be provided when warranted .

A note on gastrointestinal irritation Gastrointestinal irritation may also occur. Rarely, esophagitis and esophageal ulcers have been reported in patients receiving doxycycline. Most of these patients took medication immediately before going to bed. Administration of appropriate amounts of fluid with the tablets is recommended to reduce the risk of esophageal irritation and ulceration, and late evening ingestion of the dose should be avoided . To decrease the risk of gastric irritation, it is recommended that doxycycline is taken with food or milk. The absorption of doxycycline is not significantly influenced by simultaneous ingestion of food or milk .

Pregnancy Results of animal research indicate that tetracyclines cross the placenta, are found in fetal tissues and exert toxic effects on the developing fetus, manifested by retardation of skeletal development. The importance of this in humans is not known, however, doxycycline should not be used in pregnant women unless the benefit significantly outweighs the risk .

Carcinogenicity In vivo studies conducted in rats and mice have not provided conclusive evidence that tetracyclines may be carcinogenic or that they affect fertility. In two mammalian cell lines, positive tests for mutagenicity occurred at concentrations of 60 and 10 mcg/ml respectively. In humans, no association between tetracyclines and these effects have been established .

Precaution

During development of teeth (last trimester of pregnency, upto 12 yrs of age) the use of tetracyclines may lead to discoloration of teeth. So tetracyclines should not be administered during these periods

Interaction

Should not be taken with antacids, milk, other alkalis e.g. calcium, magnesium and iron, penicillin, anticoagulants, anti-diabetic agents, anticonvulsants and enzyme inducing drugs.

Volume of Distribution

Doxycycline diffuses readily into most body tissues, fluid and/or cavities and the volume of distribution has been measured as 0.7 L/kg .

Elimination Route

Tetracyclines, such as doxycycline, are readily absorbed and are bound to plasma proteins by varying degrees. Doxycycline is almost completely absorbed after oral administration. This drug is highly lipid soluble and has a low affinity for calcium binding . Absorption is not significantly affected by the concomitant ingestion of food or milk . Peak serum levels of approximately 2.6 mcg/ml are reached at 2 hours following a 200 mg tablet oral dose .

Half Life

16.33 hr (± 4.53 sd) .

Clearance

The excretion of doxycycline by the kidney is about 40% over 72 hours in individuals with normal kidney function (creatinine clearance approximately 75 mL/min). This rate may fall as low as 1-5% over 72 hours in individuals with severe renal insufficiency (creatinine clearance below 10 mL/min). Some clinical studies have shown no major difference in serum half-life of doxycycline (range 18-22 hours) in patients with normal and severely impaired renal function. Hemodialysis does not affect serum half-life of doxycycline .

Elimination Route

Mainly the urine and feces as active and unchanged drug . Between 40% and 60% of an administered dose can be accounted for in the urine by 92 hours, and approximately 30% can be accounted for in the feces .

Pregnancy & Breastfeeding use

Pregnancy: Doxycycline should be avoided in pregnant women, because of the risk of both staining and effect on bone growth in the fetus.

Lactation: Doxycyclines enter breast milk, and mothers taking these drugs should not breastfeed their child.

Contraindication

Hypersensitivity to doxycycline and any of the tetracyclines. Concurrent use with methoxyflurane. Lactation

Special Warning

Neonates and children: Doxycycline may cause permanent discoloration of the teeth and so is contraindicated for neonates and children under 12 years.

Elderly: No special precautions are necessary in the elderly.

Storage Condition

It should be stored in a dry place at room temperature.

Innovators Monograph

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