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 the following gram-negative microorganisms: chancroid caused by haemophilus ducreyi. plague due to yersinia pestis. tularemia due to francisella tularensis. cholera caused by vibrio cholerae. campylobacter fetus infections caused by campylobacter fetus. brucellosis due to brucella species (in conjunction with streptomycin). bartonellosis due to bartonella bacilliformis. granuloma inguinale caused by calymmatobacterium granulomatis. because many strains of the following groups of microorganisms have been shown to be resistant to doxycycline, culture and susceptibility testing are recommended. doxycycline is indicated for treatment of infections caused by the following gram-negative microorganisms, when bacteriologic testing indicates appropriate susceptibility to the drug: escherichia coli enterobacter aerogenes shigella species acinetobacter species respiratory tract infections caused by haemophilus influenzae. respiratory tract and urinary tract infections caused by klebsiella species. doxycycline is indicated for treatment of infections caused by the following gram-positive microorganisms when bacteriologic testing indicates appropriate susceptibility to the drug: upper respiratory infections caused by streptococcus pneumoniae. anthrax due to bacillus anthracis, including inhalational anthrax (post-exposure): to reduce the incidence or progression of disease following exposure to aerosolized bacillus anthracis. when penicillin is contraindicated, doxycycline is an alternative drug in the treatment of the following infections: uncomplicated gonorrhea caused by neisseria gonorrhoeae. syphilis caused by treponema pallidum. yaws caused by treponema pertenue. listeriosis due to listeria monocytogenes. vincent's infection caused by fusobacterium fusiforme. actinomycosis caused by actinomyces israelii. infections caused by clostridium species. in acute intestinal amebiasis, doxycycline may be a useful adjunct to amebicides. in severe acne, doxycycline may be useful adjunctive therapy.

xin 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 diarrhea following antibiotic use. careful medical history is necessary since cdad has been reported to occur over two months after the administration of antibacterial agents. if cdad is suspected or confirmed, ongoing antibiotic use not directed against c. difficile may need to be discontinued. appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of c. difficile, and surgical evaluation should be instituted as clinically indicated. all tetracyclines form a stable calcium complex in any bone-forming tissue. a decrease in the fibula growth rate has been observed in prematures given oral tetracycline in doses of 25 mg/kg every six hours. this reaction was shown to be reversible when the drug was discontinued. results of animal studies indicate that tetracyclines cross the placenta, are found in fetal tissues, and can have toxic effects on the developing fetus (often related to retardation of skeletal development). evidence of embryo toxicity has been noted in animals treated early in pregnancy. if any tetracycline is used during pregnancy or if the patient becomes pregnant while taking these drugs, the patient should be apprised of the potential hazard to the fetus. the antianabolic action of the tetracyclines may cause an increase in bun. studies to date indicate that this does not occur with the use of doxycycline in patients with impaired renal function. photosensitivity manifested by an exaggerated sunburn reaction has been observed in some individuals taking tetracyclines. patients apt 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.

body weight may be used. for pediatric patients over 100 pounds the usual adult dose should be used. uncomplicated gonococcal infections in adults (except anorectal infections in men) 100 mg, by mouth, twice a day for 7 days. as an alternate single visit dose, administer 300 mg stat followed in one hour by a second 300 mg dose. acute epididymo-orchitis caused by n. gonorrhoeae 100 mg, by mouth, twice a day for at least 10 days. primary and secondary syphilis 300 mg a day in divided doses for at least 10 days. uncomplicated urethral, endocervical, or rectal infection in adults caused by chlamydia trachomatis 100 mg, by mouth, twice a day for at least 7 days. nongonococcal urethritis caused by c. trachomatis and u. urealyticum 100 mg, by mouth, twice a day for at least 7 days. acute epididymo-orchitis caused by c. trachomatis 100 mg, by mouth, twice a day for at least 10 days. inhalational anthrax (post-exposure) adults: 100 mg of doxycycline, by mouth, twice a day for 60 days. children: weighing less than 100 pounds (45 kg); 1 mg/lb (2.2 mg/kg) of body weight, by mouth, twice a day for 60 days. children weighing 100 pounds or more should receive the adult dose. when used in streptococcal infections, therapy should be continued for 10 days. administration of adequate amounts of fluid along with capsule and tablet forms of drugs in the tetracycline class is recommended to wash down the drugs and reduce the risk of esophageal irritation and ulceration. (see adverse reactions.) if gastric irritation occurs, doxycycline may be given with food. ingestion of a high fat meal has been shown to delay the time to peak plasma concentrations by an average of one hour and 20 minutes. however, in the same study, food enhanced the average peak concentration by 7.5% and the area under the curve by 5.7%.

common. photosensitivity is discussed above. (see warnings.) renal toxicity rise in bun has been reported and is apparently dose related. (see warnings.) 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 with tetracyclines. other intracranial hypertension (ih, pseudotumor cerebri) has been associated with the use of tetracyclines. (see precautions general.) when given over prolonged periods, tetracyclines have been reported to produce brown-black microscopic discoloration of the thyroid gland. no abnormalities of thyroid function are known to occur.

duals with severe renal insufficiency (creatinine clearance below 10 ml/min). studies have shown no significant difference in serum half-life of doxycycline (range 18 to 22 hours) in individuals with normal and severely impaired renal function. hemodialysis does not alter serum half-life. microbiology mechanism of action doxycycline inhibits bacterial protein synthesis by binding to the 30s ribosomal subunit. doxycycline has bacteriostatic activity against a broad range of gram-positive and gram-negative bacteria. cross resistance with other tetracyclines is common. doxycycline has been shown to be active against most isolates of the following microorganisms, both in vitro and in clinical infections as described in the indications and usage section of the package insert. gram-negative bacteria acinetobacter species bartonella bacilliformis brucella species enterobacter aerogenes escherichia coli francisella tularensis haemophilus ducreyi haemophilus influenzae klebsiella granulomatis klebsiella species neisseria gonorrhoeae shigella species vibrio cholerae vibrio fetus yersinia pestis gram-positive bacteria bacillus anthracis streptococcus pneumoniae anaerobes clostridium species fusobacterium fusiforme propionibacterium acnes other bacteria nocardiae and other aerobic actinomyces species borrelia recurrentis chlamydophila psittaci chlamydia trachomatis mycoplasma pneumoniae rickettsiae treponema pallidum treponema pallidum subspecies pertenue ureaplasma urealyticum parasites balantidium coli entamoeba species plasmodium falciparum* *doxycycline has been found to be active against the asexual erythrocytic forms of plasmodium falciparum, but not against the gametocytes of p. falciparum. the precise mechanism of action of the drug is not known. susceptibility testing methods when available, the clinical microbiology laboratory should provide the results of in vitro susceptibility test results for antimicrobial drugs used in resident hospitals to the physician as periodic reports that describe the susceptibility profile of nosocomial and community-acquired pathogens. these reports should aid the physician in selecting the most effective antimicrobial. dilution techniques quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (mics). these mics provide estimates of the susceptibility of bacteria to antimicrobial compounds. the mics should be determined using a standardized test method (broth and/or agar).1,2,4,6,7the mic values should be interpreted according to criteria provided in table 1. diffusion techniques quantitative methods that require measurement of zone diameters can also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. the zone size provides an estimate of the susceptibility of bacteria to antimicrobial compounds. the zone size should be determined using a standard test method.1,3,4 this procedure uses paper disks impregnated with 30 mcg doxycycline to test the susceptibility of bacteria to doxycycline. the disk diffusion interpretive criteria are provided in table 1. anaerobic techniques for anaerobic bacteria, the susceptibility to doxycycline can be determined by a standardized test method.5 the mic values obtained should be interpreted according to the criteria provided in table 1. table 1: susceptibility test interpretive criteria for doxycycline and tetracycline * organisms susceptible to tetracycline are also considered susceptible to doxycycline. however, some organisms that are intermediate or resistant to tetracycline may be susceptible to doxycycline. † the current absence of resistance isolates precludes defining any results other than “susceptible”. if isolates yielding mic results other than susceptible, they should be submitted to a reference laboratory for further testing. ‡ gonococci with 30 mcg tetracycline disk zone diameters of <19 mm usually indicate a plasmid-mediated tetracycline resistant neisseria gonorrhoeae isolate. resistance in these strains should be confirmed by a dilution test (mic ≥ 16 mcg/ml). bacteria* minimal inhibitory concentration (mcg/ml) zone diameter (mm) agar dilution (mcg/ml) s i r s i r s i r acinetobacter spp. doxycycline ≤4 8 ≥16 ≥13 10 to 12 ≤9 - - - tetracycline ≤4 8 ≥16 ≥15 12 to 14 ≤11 - - - anaerobes tetracycline - - - - - - ≤4 8 ≥16 bacillus anthracis† doxycycline ≤1 - - - - - - - - tetracycline ≤1 - - - - - - - - brucella species† doxycycline ≤1 - - - - - - - - tetracycline ≤1 - - - - - - - - enterobacteriaceae doxycycline ≤4 8 ≥16 ≥14 11 to 13 ≤10 - - - tetracycline ≤4 8 ≥16 ≥15 12 to 14 ≤11 - - - franciscella tularensis† doxycycline ≤4 - - - - - - - - tetracycline ≤4 - - - - - - - - haemophilus influenzae tetracycline ≤2 4 ≥8 ≥29 26 to 28 ≤25 - - - mycoplasma pneumoniae† tetracycline - - - - - - ≤2 - - neisseria gonorrhoeae‡ tetracycline - - - ≥38 31 to 37 ≤30 ≤0.25 0.5 to 1 ≥2 norcardiae and other aerobic actinomyces species doxycycline ≤1 2 to 4 ≥8 - - - - - - streptococcus pneumoniae doxycycline ≤ 0.25 0.5 > 1 > 28 25 to 27 < 24 - - - tetracycline <1 2 > 4 > 28 25 to 27 < 24 - - - vibrio cholerae doxycycline ≤4 8 ≥16 - - - - - - tetracycline ≤4 8 ≥16 - - - - - - yersinia pestis doxycycline ≤4 8 ≥16 - - - - - - tetracycline ≤4 8 ≥16 - - - - - - ureaplasma urealyticum tetracycline - - - - - - ≤1 - ≥2 a report of susceptible (s) indicates that the antimicrobial is likely to inhibit growth of the pathogen if the antimicrobial compound reaches the concentrations at the infection site necessary to inhibit growth of the pathogen. a report of intermediate (i) indicates that the result should be considered equivocal, and, if the bacteria is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. this category implies possible clinical applicability in body sites where the drug product is physiologically concentrated or in situations where high dosage of drug can be used. this category also provides a buffer zone that prevents small uncontrolled technical factors from causing major discrepancies in interpretation. a report of resistant (r) indicates that the pathogen is not likely to inhibit growth of the pathogen if the antimicrobial compound reaches the concentrations usually achievable at the infection site; other therapy should be selected. quality control standardized susceptibility test procedures require the use of laboratory controls to monitor and ensure the accuracy and precision of supplies and reagents used in the assay, and the techniques of the individuals performing the test.1,2,3,4,5,6,7 standard doxycycline and tetracycline powders should provide the following range of mic values noted in table 2. for the diffusion technique using the 30 mcg doxycycline disk the criteria in table 2 should be achieved. table 2: acceptable quality control ranges for susceptibility testing for doxycycline and tetracycline qc strain minimal inhibitory concentration (mcg/ml) zone diameter (mm) agar dilution (mcg/ml) enterococcus faecalis atcc 29212 doxycycline 2 to 8 - - tetracycline 8 to 32 - - escherichia coli atcc 25922 doxycycline 0.5 to 2 18 to 24 - tetracycline 0.5 to 2 18 to 25 - eggerthella lenta atcc 43055 doxycycline 2 to 16 - - haemophilus influenzae atcc 49247 tetracycline 4 to 32 14 to 22 - neisseria gonorrhoeae atcc 49226 tetracycline - 30 to 42 0.25 to 1 staphylococcus aureus atcc 25923 doxycycline - 23 to 29 - tetracycline - 24 to 30 - staphylococcus aureus atcc 29213 doxycycline 0.12 to 0.5 - - tetracycline 0.12 to 1 - - streptococcus pneumoniae atcc 49619 doxycycline 0.015 to 0.12 25 to 34 - tetracycline 0.06 to 0.5 27 to 31 - bacteroides fragilis atcc 25285 tetracycline - - 0.12 to 0.5 bacteroides thetaiotaomicron atcc 29741 doxycycline 2 to 8 - - tetracycline - - 8 to 32 mycoplasma pneumoniae atcc 29342 tetracycline 0.06 to 0.5 - 0.06 to 0.5 ureaplasma urealyticum atcc 33175 tetracycline - - ≥ 8

ydrate usp equivalent to 100 mg doxycycline. doxycycline capsules usp, 100 mg is available in: bottle of 50 capsules ndc 68180-652-08 bottle of 250 capsules ndc 68180-652-29 store at 25°c (77°f); excursions permitted to 15 to 30°c (59 to 86°f) [see usp controlled room temperature]. protect from light. dispense in a tight, light-resistant container as defined in the usp/nf.