Актуальная Медицина - Doxycycline

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Doxycycline 


Description:

Doxycycline is a broad-spectrum antibiotic synthetically derived from oxytetracycline and is available as doxycycline monohydrate, doxycycline hyclate, doxycycline hydrochloride hemiethanolate hemihydrate and doxycycline calcium for oral administration. It is also available as doxycycline hyclate for intravenous use as well as coated hyclate pellets.

Clinical Pharmacology:

Tetracyclines are readily absorbed and are bound to plasma proteins in varying degree. They are concentrated by the liver in the bile, and excreted in the urine and feces at high concentrations and in a biologically active form. Doxycycline is virtually completely absorbed after oral administration.

Microbiology:

The tetracyclines are primarily bacteriostatic and are thought to exert their antimicrobial effect by the inhibition of protein synthesis.

Indications and Usage:

Doxycycline is indicated for the treatment of the following infections:

·      Rocky mountain spotted fever, typhus fever and the typhus group, Q fever, rickettsialpox, and tick fevers caused by Rickettsiae.

·      Respiratory tract infections caused by Mycoplasma pneumoniae.

·      Lymphogranuloma venereum caused by Chlamydia trachomatis.

·      Psittacosis (ornithosis) caused by Chlamydia psittaci.

·      Trachoma caused by Chlamydia trachomatis, although the infectious agent is not always eliminated as judged by immunofluorescence.

·      Inclusion conjunctivitis caused by Chlamydia trachomatis.

·      Uncomplicated urethral, endocervical or rectal infections in adults caused by Chlamydia trachomatis.

·      Nongonococcal urethritis caused by Ureaplasma urealyticum.

·      Relapsing fever due to Borrelia recurrentis.

·      Doxycycline is also indicated for the treatment of infections caused by  gram-negative microorganisms.

Contraindications:

This drug is contraindicated in persons who have shown hypersensitivity to any of the tetracyclines.

Warnings:

THE USE OF DRUGS OF THE TETRACYCLINE CLASS DURING TOOTH DEVELOPMENT (LAST HALF OF PREGNANCY, INFANCY AND CHILDHOOD TO THE AGE OF 8 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 it has been observed following repeated short-term courses. Enamel hypoplasia has also been reported. TETRACYCLINE DRUGS, THEREFORE, SHOULD NOT BE USED IN THIS AGE GROUP UNLESS OTHER DRUGS ARE NOT LIKELY TO BE EFFECTIVE OR ARE CONTRAINDICATED.

Precautions:

General

As with other antibiotic preparations, use of this drug may result in overgrowth of nonsusceptible organisms, including fungi. If superinfection occurs, the antibiotic should be discontinued and appropriate therapy instituted.

Bulging fontanels in infants and benign intracranial hypertension in adults have been reported in individuals receiving tetracyclines. These conditions disappeared when the drug was discontinued.

Incision and drainage or other surgical procedures should be performed in conjunction with antibiotic therapy, when indicated.

Information for Patients

Patients taking doxycycline for malaria prophylaxis should be advised:

·         that no present-day antimalarial agent, including doxycycline, guarantees protection against malaria.

·         to avoid being bitten by mosquitoes by using personal protective measures that help avoid contact with mosquitoes, especially from dusk to dawn (e.g., staying in well-screened areas, using mosquito nets, covering the body with clothing, and using an effective insect repellent.

·         that doxycycline prophylaxis:

- should begin 1-2 days before travel to the malarious area.

- should be continued daily while in the malarious area and after leaving the malarious area.

- should be continued for 4 further weeks to avoid development of malaria after returning from an endemic area.

- should not exceed 4 months.

All patients taking doxycycline should be advised:

·         to avoid excessive sunlight or artificial ultraviolet light while receiving doxycycline and to discontinue therapy if phototoxicity (e.g., skin eruption, etc.) occurs. Sunscreen or sunblock should be considered.

·         to drink fluids liberally along with doxycycline to reduce the risk of esophageal irritation and ulceration.

·         that the absorption of tetracyclines is reduced when taken with foods, especially those which contain calcium. However, the absorption of doxycycline is not markedly influenced by simultaneous ingestion of food or milk. 

·         that the absorption of tetracyclines is reduced when taking bismuth subsalicylate.

·         that the use of doxycycline might increase the incidence of vaginal candidiasis.

Pregnancy Category D

Labor and Delivery

The effect of tetracyclines on labor and delivery is unknown.

Nursing Mothers

Tetracyclines are excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from doxycycline, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Drug Interactions:

Because 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 tetracyclines in conjunction with penicillin.

 

Adverse Reactions:

Due to oral doxycycline's virtually complete absorption, side effects of the lower bowel, particularly diarrhea, have been infrequent. The following adverse reactions have been observed in patients receiving tetracyclines:

Gastrointestinal: anorexia, nausea, vomiting, diarrhea, glossitis, dysphagia, enterocolitis, and inflammatory lesions (with monilial overgrowth) in the anogenital region. Hepatotoxicity has been reported rarely. These reactions have been caused by both the oral and parenteral administration of tetracyclines. Rare instances of esophagitis and esophageal ulcerations have been reported in patients receiving capsule and tablet forms of the drugs in the tetracycline class. Most of these patients took medications immediately before going to bed.

Skin: maculopapular and erythematous rashes. Exfoliative dermatitis has been reported but is uncommon. Photosensitivity is discussed above.

Renal toxicity: rise in BUN has been reported and is apparently dose related.

Hypersensitivity reactions: urticaria, angioneurotic edema, anaphylaxis, anaphylactoid purpura, serum sickness, pericarditis, and exacerbation of systemic lupus erythematosus.

Blood: Hemolytic anemia, thrombocytopenia, neutropenia, and eosinophilia have been reported.

Other: bulging fontanels in infants and intracranial hypertension in adults. 

When given over prolonged periods, tetracyclines have been reported to produce brown-black microscopic discoloration of the thyroid gland. No abnormalities of thyroid function studies are known to occur.

Overdosage:

In case of overdosage, discontinue medication, treat symptomatically, and institute supportive measures. Dialysis does not alter serum half-life and thus would not be of benefit in treating cases of overdosage.

Dosage and Administration:

Syrup, Capsules, Oral Suspension and Tablets

THE USUAL DOSAGE AND FREQUENCY OF ADMINISTRATION OF DOXYCYCLINE DIFFERS FROM THAT OF THE OTHER TETRACYCLINES. EXCEEDING THE RECOMMENDED DOSAGE MAY RESULT IN AN INCREASED INCIDENCE OF SIDE EFFECTS.

Adults: The usual dose of oral


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