It is used in prophylaxis against malaria. It should not be used alone for initial treatment of malaria, even when the parasite is doxycycline-sensitive, because the antimalarial effect of doxycycline is delayed. This delay is related to its mechanism of action, which is to specifically impair the progeny of the apicoplast genes, resulting in their abnormal cell division.
It can be used in a treatment plan in combination with other agents, such as quinine.
Some Gram-positive bacteria have developed resistance to doxycycline. Up to 44% of Streptococcus pyogenes and up to 74% of S. faecalis specimens have developed resistance to the tetracycline group of antibiotics. When bacteriologic testing indicates appropriate susceptibility to the drug, doxycycline may be used to treat these infections caused by Gram-positive bacteria:
Doxycycline has been used successfully to treat sexually transmitted, respiratory, and ophthalmic infections. Representative pathogenic genera include Chlamydia, Streptococcus, Ureaplasma, Mycoplasma, and others. The following represents MIC susceptibility data for a few medically significant microorganisms.
Cautions and side effects are similar to those of other members of the tetracycline antibiotic group.
An erythematous rash in sun-exposed parts of the body has been reported to occur in 7.3–21.2% of persons taking doxycycline for malaria prophylaxis. One study examined the tolerability of various malaria prophylactic regimens and found doxycycline did not cause a significantly higher percentage of all skin events (photosensitivity not specified) when compared with other antimalarials. The rash resolves upon discontinuation of the drug.
Unlike some other members of the tetracycline group, it may be used in those with renal impairment. Doxycycline is contraindicated in the pediatric treatment of acute bacterial rhinosinusitis.
The combination of doxycycline with dairy, antacids, calcium supplements, iron products, and laxatives containing magnesium is not inherently dangerous, but any of these foods and supplements may decrease doxycycline's effectiveness.[verification needed]
Previously, doxycycline was believed to impair 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 antibiotics (including doxycycline), although many physicians still recommend the use of barrier contraception for people taking the drug to prevent unwanted pregnancy.
Pregnancy and lactation
Doxycycline is categorized by the FDA as a class D drug in pregnancy. As with all tetracycline antibiotics, it is contraindicated in pregnancy through infancy and childhood up to eight years of age, due to the potential for disrupting bone and tooth development. Therefore, doxycycline should not be administered to children under the age of eight except in the treatment of anthrax, or where other medications are contraindicated or ineffective.
Doxycycline crosses into breastmilk. The adverse effects on teeth and long bones of children directly administered tetracycline antibiotics is documented, but these effects have not been recorded in infants exposed through breastmilk. Although the dose an infant would receive through breastfeeding would likely be minimal, a theoretical risk exists.
Doxycycline–metal ion complexes are unstable at acid pH, therefore more doxycycline enters the duodenum for absorption compared with the earlier tetracycline compounds. In addition, food has less effect on absorption than on absorption of earlier drugs with doxycycline serum concentrations being reduced by about 20% by test meals compared with 50% for tetracycline.
Physical and chemical properties
Expired tetracyclines or tetracyclines allowed to stand at a pH less than 2 are reported to be nephrotoxic due to the formation of a degradation product, anhydro-4-epitetracycline causing Fanconi syndrome. In the case of doxycycline, the absence of a hydroxyl group in C-6 prevents the formation of the nephrotoxic compound. Nevertheless, tetracyclines and doxycycline itself have to be taken with precaution in patients with kidney injury, as they can worsen azotemia due to catabolic effects.
Tet-ON inducible shRNA system
At subantimicrobial doses, doxycycline is an inhibitor of matrix metalloproteases, and has been used in various experimental systems for this purpose, such as for recalcitrant recurrent corneal erosions. Doxycycline has been demonstrated to reduce the in vitro growth of human breast and prostate cancer cells, possibly through G1 phase cell cycle arrest. Doxycycline and other tetracyclines are also highly osteotropic, and in animal models of breast cancer bone metastases, doxycycline treatments have reduced the growth of breast cancer tumours in the bone. Doxycycline has been used successfully in the treatment of one patient with lymphangioleiomyomatosis, an otherwise progressive and fatal disease. It has also been shown to attenuate cardiac hypertrophy (in mice), a deadly consequence of prolonged hypertension. In chronic obstructive pulmonary disease, doxycycline has been shown to improve lung functions in patients with stable symptoms. Doxycycline is also used in "tet-on" and "tet-off" tetracycline-controlled transcriptional activation to regulate transgene expression in organisms and cell cultures.
Treatment of filariasis and onchocerciasis due to filariae and onchocercae (in general, harbouring endosymbiotic Wolbachia bacteria, doxycycline kills the bacteria, and (by removal of the endosymbiotes) the nematodes)
Doxycycline is a semisynthetic tetracycline invented and clinically developed in the early 1960s by Pfizer Inc. and marketed under the brand name Vibramycin.
Despite having been on the market for decades and facing no known ingredient shortages, the market price for the generic version of doxycycline increased in price in the United States by 9,245% between October 2013 and April 2014. This was the subject of a congressional investigation by Representative Elijah E. Cummings, the ranking member of the House Committee on Oversight and Government Reform, and Senator Bernard Sanders, chairman of the Senate Subcommittee on Primary Health and Aging.
^Sweet RL, Schachter J, Landers DV, Ohm-Smith M, Robbie MO (1988). "Treatment of hospitalized patients with acute pelvic inflammatory disease: comparison of cefotetan plus doxycycline and ana doxycycline". Am. J. Obstet. Gynecol.158 (3 Pt 2): 736–41. PMID3162653.
^Määttä M, Kari O, Tervahartiala T et al. (2006). "Tear fluid levels of MMP-8 are elevated in ocular rosacea--treatment effect of oral doxycycline". Graefes Arch. Clin. Exp. Ophthalmol.244 (8): 957–62. doi:10.1007/s00417-005-0212-3. PMID16411105.
^Quarterman MJ, Johnson DW, Abele DC, Lesher JL, Hull DS, Davis LS (1997). "Ocular rosacea. Signs, symptoms, and tear studies before and after treatment with doxycycline". Arch Dermatol133 (1): 49–54. doi:10.1001/archderm.133.1.49. PMID9006372.
^Walker DH, Paddock CD, Dumler JS (November 2008). "Emerging and re-emerging tick-transmitted rickettsial and ehrlichial infections". Med. Clin. North Am.92 (6): 1345–61, x. doi:10.1016/j.mcna.2008.06.002. PMID19061755.
^Nadelman RB, Luger SW, Frank E, Wisniewski M, Collins JJ, Wormser GP (1992). "Comparison of cefuroxime axetil and doxycycline in the treatment of early Lyme disease". Annals of Internal Medicine117 (4): 273–80. doi:10.7326/0003-4819-117-4-273. PMID1637021.
^Karlsson M, Hammers-Berggren S, Lindquist L, Stiernstedt G, Svenungsson B (1994). "Comparison of intravenous penicillin G and oral doxycycline for treatment of Lyme neuroborreliosis". Neurologe44 (7): 1203–7. doi:10.1212/WNL.44.7.1203. PMID8035916.
^Karlsson U, Bjöersdorff A, Massung RF, Christensson B (2001). "Human granulocytic ehrlichiosis--a clinical case in Scandinavia". Scand. J. Infect. Dis.33 (1): 73–4. doi:10.1080/003655401750064130. PMID11234985.
^Hoerauf A, Mand S, Fischer K et al. (2003). "Doxycycline as a novel strategy against bancroftian filariasis-depletion of Wolbachia endosymbionts from Wuchereria bancrofti and stop of microfilaria production". Med. Microbiol. Immunol.192 (4): 211–6. doi:10.1007/s00430-002-0174-6. PMID12684759.
^Taylor MJ, Makunde WH, McGarry HF, Turner JD, Mand S, Hoerauf A (2005). "Macrofilaricidal activity after doxycycline treatment of Wuchereria bancrofti: a double-blind, randomised placebo-controlled trial". Lancet365 (9477): 2116–21. doi:10.1016/S0140-6736(05)66591-9. PMID15964448.
^Mylonas, I (Jan 2011). "Antibiotic chemotherapy during pregnancy and lactation period: aspects for consideration.". Archives of gynecology and obstetrics283 (1): 7–18. doi:10.1007/s00404-010-1646-3. PMID20814687.
^ abFoye's Principles of Medicinal Chemistry; David A. Williams; William O. Foye, Thomas L. Lemke
^ abGoodman & Gilman's The Pharmacological Basis of Therapeutics, 12ed, Laurence L. Brunton, Bruce A. Chabner, Björn C. Knollmann
^Dursun D, Kim MC, Solomon A, Pflugfelder SC (2001). "Treatment of recalcitrant recurrent corneal erosions with inhibitors of matrix metalloproteinase-9, doxycycline and corticosteroids". Am. J. Ophthalmol.132 (1): 8–13. doi:10.1016/S0002-9394(01)00913-8. PMID11438047.
^Duivenvoorden, W. C.; Hirte, H. W.; Singh, G. (1997). "Use of tetracycline as an inhibitor of matrix metalloproteinase activity secreted by human bone-metastasizing cancer cells". Invasion & metastasis17 (6): 312–322. PMID9949290. edit
^Fife, R. S.; Sledge Jr, G. W. (1995). "Effects of doxycycline on in vitro growth, migration, and gelatinase activity of breast carcinoma cells". The Journal of laboratory and clinical medicine125 (3): 407–411. PMID7897308. edit
^Duivenvoorden, W. C.; Popović, S. V.; Lhoták, S.; Seidlitz, E.; Hirte, H. W.; Tozer, R. G.; Singh, G. (2002). "Doxycycline decreases tumor burden in a bone metastasis model of human breast cancer". Cancer research62 (6): 1588–1591. PMID11912125. edit
^Moses MA, Harper J, Folkman J (2006). "Doxycycline treatment for lymphangioleiomyomatosis with urinary monitoring for MMPs". N. Engl. J. Med.354 (24): 2621–2. doi:10.1056/NEJMc053410. PMID16775248.
^Errami M, Galindo CL, Tassa AT, Dimaio JM, Hill JA, Garner HR (2007). "Doxycycline attenuates isoproterenol- and transverse aortic banding- induced cardiac hypertrophy in mice". J Pharmacol Exp Ther324 (3): 1196–203. doi:10.1124/jpet.107.133975. PMID18089841.
^Saraiva IH, Jones RN, Erwin M, Sader HS (1997). "[Evaluation of antimicrobial sensitivity of 87 clinical isolates of vancomycin-resistant enterococci]". Rev Assoc Med Bras (in Portuguese) 43 (3): 217–22. doi:10.1590/S0104-42301997000300009. PMID9497549.
^Dibb WL, Digranes A (1981). "Characteristics of 20 human Pasteurella isolates from animal bite wounds". Acta Pathol Microbiol Scand [B]89 (3): 137–41. PMID7315339.
^Raza M, Ballering JG, Hayden JM, Robbins RA, Hoyt JC (2006). "Doxycycline decreases monocyte chemoattractant protein-1 in human lung epithelial cells". Exp. Lung Res.32 (1–2): 15–26. doi:10.1080/01902140600691399. PMID16809218.
^Chodosh S, Tuck J, Pizzuto D (1988). "Comparative trials of doxycycline versus amoxicillin, cephalexin and enoxacin in bacterial infections in chronic bronchitis and asthma". Scand J Infect Dis Suppl53: 22–8. PMID3047855.
^Minagar, A.; Alexander, J. S.; Schwendimann, R. N.; Kelley, R. E.; Gonzalez-Toledo, E.; Jimenez, J. J.; Mauro, L.; Jy, W.; Smith, S. J. (2008). "Combination Therapy with Interferon Beta-1a and Doxycycline in Multiple Sclerosis: An Open-Label Trial". Archives of Neurology65 (2): 199–204. doi:10.1001/archneurol.2007.41. PMID18071030. edit