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Doxycycline

[dok-see-sahy-kleen, -klin]

Doxycycline (INN) is a member of the tetracycline antibiotics group and is commonly used to treat a variety of infections. Doxycycline is a semi-synthetic tetracycline invented and clinically developed in the early 1960s by Pfizer Inc. and marketed under the brand name Vibramycin. Vibramycin received FDA approval in 1967, becoming Pfizer's first once-a-day broad-spectrum antibiotic. Other brand names include Monodox, Periostat, Vibra-Tabs, Doryx, Vibrox, Adoxa, Doxyhexal and Atridox (topical doxycycline hyclate for Periodontitis).

Indicated uses

As well as the general indications for all members of the tetracycline antibiotics group, Doxycycline is frequently used to treat chronic prostatitis, sinusitis, syphilis, chlamydia, pelvic inflammatory disease, acne and rosacea. In addition it is used in the treatment and prophylaxis of Bacillus anthracis (anthrax) and in prophylaxis against malaria. It should not be used alone for initial treatment of malaria, even when the parasite is doxycyline-sensitive, because the antimalarial effect of doxycyline is delayed. This delay is related to its mechanism of action. Its mechanism of action against malaria is to specifically impair in the progeny the apicoplast genes resulting in their abnormal cell division.

It is also effective against Yersinia pestis (the infectious agent of bubonic plague) and is prescribed for the treatment of Lyme disease,, ehrlichiosis and Rocky Mountain spotted fever. In fact, because doxycycline is one of the few medications that are effective in treating Rocky Mountain spotted fever (with the next best alternative being chloramphenicol), doxycycline is indicated even in use in children for this illness. Otherwise, doxycycline is not indicated in the use in children under the age of 8 years. Doxycycline, like other antibiotics, will not work for colds, flu, or other viral infections.

Elephantiasis is a disease caused by a nematode (worm) Wuchereria bancrofti. It causes swollen limbs and genitals (Filariasis) and affects over 120 million people in the world. Previous anti-nematode treatments have been limited by poor levels of effectiveness, drug side effects and high costs. Doxycycline was shown in 2003 to kill the symbiotic Wolbachia bacteria upon which the nematodes are dependent. Field trials in 2005 showed that Doxycycline almost completely eliminates blood-borne filaria when given for an 8 week course.

When bacteriologic testing indicates appropriate susceptibility to the drug, doxycycline may be used to treat and prevent:

Escherichia coli
Enterobacter aerogenes (formerly Aerobacter aerogenes)
Lyme Disease
folliculitis
Acne
Shigella species
Acinetobacter species (formerly Mima species and Herellea species)
Respiratory tract infections caused by Haemophilus influenzae
Respiratory tract and urinary tract infections
Upper respiratory infections caused by Streptococcus pneumoniae (formerly Diplococcus pneumoniae)
Methicillin-resistant Staphylococcus aureus (MRSA) infections

Cautions and side effects

Cautions and side effects are similar to other members of the tetracycline antibiotic group. However the 10% risk of photosensitivity skin reactions is of particular importance for those intending long-term use for malaria prophylaxis. Reports of GERD have been cited with the use of doxycycline.

Unlike some other members of the tetracycline group, it may be used in those with renal impairment.

Previously, it was believed that doxycycline impairs the effectiveness of many types of hormonal contraception due to CYP450 induction. Recent research has shown no significant loss of effectiveness in oral contraceptives while using most tetracycline antibiotic (including doxycycline), although many physicians still recommend the use of barrier contraception for people taking the drug to prevent unwanted pregnancy.

It should be taken with a full glass of water and patients should be upright for at least 30 minutes after administration to prevent irritation of the esophagus and stomach. Also, there is a slim risk of liver damage during prolonged use of the drug. It is also recommended that it be taken with a small meal of a non-dairy nature if upset stomach, nausea, or fatigue occurs.

Doxycycline is not approved for use in children under the age of 8 years for two reasons: 1) it can cause permanent yellowing or graying of the teeth, and 2), according to CDC patient information on doxycycline, it can inhibit bone growth in premature infants during the time the medication is taken; this last effect disappears when the doxycycline treatment is over. Specific exceptions are made for potentially fatal illnesses where the benefits outweigh the risks and there are few or no other alternatives, such as with Rocky Mountain spotted fever and anthrax. It should also not be used in pregnant and nursing women, as the drug can cause damage to a fetus and nursing child.

Experimental applications

At subantimicrobial doses, doxycycline is an inhibitor of matrix metalloproteinases, and has been used in various experimental systems for this purpose; such as for recalcitrant recurrent corneal erosions. Doxycycline has been used successfully in the treatment of one patient with lymphangioleiomyomatosis, an otherwise progressive and fatal disease. Doxycyline has also been shown to attenuate cardiac hypertrophy (in mice), a deadly consequence of prolonged hypertension.

Doxycycline is also used in "Tet-on" and "Tet-off" tetracycline controlled transcriptional activation to regulate transgene expression in organisms and cell cultures.

Other experimental applications include: