m-negative microorganisms: haemophilus ducreyi (chancroid), yersinia pestis francisella tularensis, bartonella bacilliformis, bacteroides species, vibrio cholerae and campylobacte fetus, brucella species (in conjunction with streptomycin). because many strains of the following groups of microorganisms have been shown to be resistant to tetracyclines, 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, haemophilus influenzae (respiratory infections), klebsiella species (respiratory and urinary infections). doxycycline is indicated for treatment of infections caused by the following gram-positive microorganisms when bacteriologic testing indicates appropriate susceptibility to the drug: streptococcus species: up to 44 percent of strains of streptococcus pyogenes and 74 percent of streptococcus faecalis have been found to be resistant to tetracycline drugs. therefore, tetracyclines should not be used for streptococcal disease unless the organism has been demonstrated to be sensitive. for upper respiratory infections due to group a beta-hemolytic streptococci, penicillin is the usual drug of choice, including prophylaxis of rheumatic fever. streptococcus pneumoniae, staphylococcus aureus, respiratory skin and soft tissue infections. tetracyclines are not the drugs of choice in the treatment of any type of staphylococcal infections. 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 infections due to: neisseria gonorrhoeae and n. meningitidis, treponema pallidum and treponema pallidum subspecies pertenue (syphilis and yaws), listeria monocytogenes, clostridium species, fusobacterium fusiforme (vincent’s infection), actinomyces species. in acute intestinal amebiasis, doxycycline may be a useful adjunct to amebicides. doxycycline is indicated in the treatment of trachoma, although the infectious agent is not always eliminated, as judged by immunofluorescence.

and b which contribute to the development of cdad. hypertoxin 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 the use of antibacterial drugs. 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 use of antibacterial drugs not directed against c. difficile may need to be discontinued. appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of c. difficile, and surgical evaluation should be instituted as clinically indicated. severe skin reactions, such as exfoliative dermatitis, erythema multiforme, stevens-johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (dress) have been reported in patients receiving doxycycline. (see adverse reactions.) if severe skin reactions occur, doxycycline should be discontinued immediately and appropriate therapy should be instituted. intracranial hypertension (ih, pseudotumor cerebri) has been associated with the use of tetracyclines including doxycycline. clinical manifestations of ih include headache, blurred vision, diplopia, and vision loss; papilledema can be found on fundoscopy. women of childbearing age who are overweight or have a history of ih are at greater risk for developing tetracycline associated ih. concomitant use of isotretinoin and doxycycline should be avoided because isotretinoin is also known to cause pseudotumor cerebri. although ih typically resolves after discontinuation of treatment, the possibility for permanent visual loss exists. if visual disturbance occurs during treatment, prompt ophthalmologic evaluation is warranted. since intracranial pressure can remain elevated for weeks after drug cessation patients should be monitored until they stabilize. 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. 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.

nt of primary and secondary syphilis, the recommended dosage is 300 mg daily for at least 10 days. in the treatment of inhalational anthrax (post-exposure) the recommended dose is 100 mg of doxycycline, twice a day. parenteral therapy is only indicated when oral therapy is not indicated and should not be continued over a prolonged period of time. oral therapy should be instituted as soon as possible. therapy must continue for a total of 60 days. pediatric patients: for all pediatric patients weighing less than 45 kg with severe or life-threatening infections (e.g., anthrax, rocky mountain spotted fever), the recommended dosage is 2.2 mg/kg of body weight administered every 12 hours. children weighing 45 kg or more should receive the adult dose. (see warnings and precautions.) for pediatric patients with less severe disease (greater than 8 years of age and weighing less than 45 kg), the recommended dosage schedule is 4.4 mg/kg of body weight divided into two doses on the first day of treatment, followed by a maintenance dose of 2.2 mg/kg of body weight (given as a single daily dose or divided into twice daily doses). for pediatric patients weighing over 45 kg, the usual adult dose should be used. in the treatment of inhalational anthrax (post-exposure) the recommended dose is 2.2 mg/kg of body weight, twice a day in children weighing less than 45 kg. parenteral therapy is only indicated when oral therapy is not indicated and should not be continued over a prolonged period of time. oral therapy should be instituted as soon as possible. therapy must continue for a total of 60 days. general: the duration of infusion may vary with the dose (100 to 200 mg per day), but is usually one to four hours. a recommended minimum infusion time for 100 mg of a 0.5 mg/ml solution is one hour. therapy should be continued for at least 24 to 48 hours after symptoms and fever have subsided. the therapeutic antibacterial serum activity will usually persist for 24 hours following recommended dosage. intravenous solutions should not be injected intramuscularly or subcutaneously. caution should be taken to avoid the inadvertent introduction of the intravenous solution into the adjacent soft tissue. preparation of solution to prepare a solution containing 10 mg/ml, the contents of the vial should be reconstituted with 10 ml (for the 100 mg/vial container) of sterile water for injection or any of the ten intravenous infusion solutions listed below. each 100 mg of doxycycline for injection (i.e., withdraw entire solution from the 100 mg vial) is further diluted with 100 ml to 1,000 ml of the intravenous solutions listed below. 1. sodium chloride injection, usp 2. 5% dextrose injection, usp 3. ringer’s injection, usp 4. invert sugar, 10% in water 5. lactated ringer’s injection, usp 6. dextrose 5% in lactated ringer’s 7. normosol-m® in d5-w (abbott) 8. normosol-r® in d5-w (abbott) 9. plasma-lyte® 56 in 5% dextrose (travenol) 10. plasma-lyte® 148 in 5% dextrose (travenol) this will result in desired concentrations of 0.1 to 1 mg/ml. concentrations lower than 0.1 mg/ml or higher than 1 mg/ml are not recommended. stability doxycycline for injection is stable for 48 hours in solution when diluted with sodium chloride injection, usp, or 5% dextrose injection, usp, to concentrations between 1 mg/ml and 0.1 mg/ml and stored at 25oc. doxycycline for injection in these solutions is stable under fluorescent light for 48 hours, but must be protected from direct sunlight during storage and infusion. reconstituted solutions (1 to 0.1 mg/ml) may be stored up to 72 hours prior to start of infusion if refrigerated and protected from sunlight and artificial light. infusion must then be completed within 12 hours. solutions must be used within these time periods or discarded. doxycycline for injection, when diluted with ringer’s injection, usp, or invert sugar, 10% in water, or normosol-m® in d5-w (abbott), or normosol-r® in d5-w (abbott), or plasma-lyte® 56 in 5% dextrose (travenol), or plasma-lyte® 148 in 5% dextrose (travenol) to a concentration between 1 mg/ml and 0.1 mg/ml, must be completely infused within 12 hours after reconstitution to ensure adequate stability. during infusion, the solution must be protected from direct sunlight. reconstituted solutions (1 to 0.1 mg/ml) may be stored up to 72 hours prior to start of infusion if refrigerated and protected from sunlight and artificial light. infusion must then be completed within 12 hours. solutions must be used within these time periods or discarded when diluted with lactated ringer’s injection, usp, or dextrose 5% in lactated ringer’s, infusion of the solution (ca. 1 mg/ml) or lower concentrations (not less than 0.1 mg/ml) must be completed within six hours after reconstitution to ensure adequate stability. during infusion, the solution must be protected from direct sunlight. solutions must be used within this time period or discarded. solutions of doxycycline for injection at a concentration of 10 mg/ml in sterile water for injection, when frozen immediately after reconstitution are stable for 8 weeks when stored at -20oc. if the product is warmed, care should be taken to avoid heating it after the thawing is complete. once thawed the solution should not be refrozen.

ura, pericarditis, exacerbation of systemic lupus erythematosus, and drug reaction with eosinophilia and systemic symptoms (dress). other: bulging fontanels in infants and intracranial hypertension in adults. (see warnings.) blood: hemolytic anemia, thrombocytopenia, neutropenia and eosinophilia have been reported. when given over prolonged periods, tetracyclines have been reported to produce brown-black microscopic discoloration of thyroid glands. no abnormalities of thyroid function studies are known to occur. to report suspected adverse reactions, contact mylan at 1-877-446-3679 (1-877-4-info-rx) or fda at 1-800-fda-1088 or www.fda.gov/medwatch.

alter this serum half-life of doxycycline. population pharmacokinetic analysis of sparse concentration-time data of doxycycline following standard of care intravenous and oral dosing in 44 pediatric patients (2 to 18 years of age) showed that allometrically-scaled clearance (cl) of doxycycline in pediatric patients ≥2 to ≤8 years of age (median [range] 3.58 [2.27 to 10.82] l/h/70 kg, n=11) did not differ significantly from pediatric patients >8 to 18 years of age (3.27 [1.11 to 8.12] l/h/70 kg, n=33). for pediatric patients weighing ≤45 kg, body weight normalized doxycycline cl in those ≥2 to ≤8 years of age (median [range] 0.071 [0.041 to 0.202] l/kg/h, n=10) did not differ significantly from those >8 to 18 years of age (0.081 [0.035 to 0.126] l/kg/h, n=8). ln pediatric patients weighing >45 kg, no clinically significant differences in body weight normalized doxycycline cl were observed between those ≥2 to ≤8 years (0.050 l/kg/h, n=l) and those >8 to 18 years of age (0.044 [0.014 to 0.121] l/kg/h, n=25). no clinically significant difference in cl between oral and iv dosing was observed in the small cohort of pediatric patients who received the oral (n=19) or iv (n=21) formulation alone. 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. resistance cross resistance with other tetracyclines is common. antimicrobial activity 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 for doxycycline for injection. gram-negative bacteria acinetobacter species bartonella bacilliformis brucella species klebsiella species klebsiella granulomatis campylobacter fetus enterobacter aerogenes escherichia coli francisella tularensis haemophilus ducreyi haemophilus influenzae neisseria gonorrhoeae shigella species vibrio cholerae yersinia pestis gram-positive bacteria bacillus anthracis listeria monocytogenes streptococcus pneumoniae anaerobic bacteria 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 for specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by fda for this drug, please see: https://www.fda.gov/stic.