DOXYCYCLINE HYCLATE- doxycycline hyclate_tablet, film coated

= 16 >= 14 11-13 <= 10 - - - Tetracycline <= 4 8 >= 16 >= 15 12-14 <= 11 - - - Franciscella tularensis Doxycycline <= 4 - - - - - - - - Tetracycline <= 4 - - - - - - - - Haemophilus influenzae Tetracycline <= 2 4 >= 8 >= 29 26-28 <= 25 - - - Mycoplasma pneumoniae Tetracycline - - - - - - <= 2 - - Neisseria gonorrhoeae 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) Tetracycline - - - >=38 31-37 <=30 <=0. 5-1 >=2 Norcardiae Actinomyces Doxycycline <=1 2-4 >=8 - - - - - - Streptococcus pneumoniae Doxycycline <=0. 5 > 1 > 28 25-27 < 24 - - - Tetracycline < 1 2 > 4 > 28 25-27 < 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 Intermediate Resistant 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 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 - 8 - - Tetracycline 8 - 32 - - Escherichia coli ATCC 25922 Doxycycline 0. 5 en dash 2 18 - 24 - Tetracycline 0. 5 - 2 18 - 25 - Eggerthella lenta Doxycycline 2 en dash 16 - - Haemophilus influenzae ATCC 49247 Tetracycline 4 - 32 14 - 22 - Neisseria gonorrhoeae ATCC 49226 Tetracycline - 30 - 42 0. 25 - 1 Staphylococcus aureus ATCC 25923 Doxycycline - 23 - 29 - Tetracycline - 24 - 30 - Staphylococcus aureus ATCC 29213 Doxycycline 0. 5 - - Tetracycline 0. 12 - 1 - - Streptococcus pneumoniae ATCC 49619 Doxycycline 0. 015 en dash 0. 12 25 - 34 - Tetracycline 0. 06 en dash 0. 5 27 - 31 - Bacteroides fragilis ATCC 25285 Tetracycline - - 0. 12 en dash 0. 5 Bacteroides thetaiotaomicron ATCC 29741 Doxycycline 2 en dash 8 - - Tetracycline - - 8 en dash 32 Mycoplasma pneumoniae ATCC 29342 Tetracycline 0. 5 Ureaplasma urealyticum ATCC 33175 Tetracycline - - >=8.
Microbiology
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 Gram-Negative Bacteria Acinetobacter Bartonella bacilliformis Brucella Enterobacter aerogenes Escherichia coli Francisella tularensis Haemophilus ducreyi Haemophilus influenzae Klebsiella granulomatis Klebsiella Neisseria gonorrhoeae Shigella Vibrio cholerae Vibrio fetus Yersinia pestis Gram-Positive Bacteria Bacillus anthracis Streptococcus pneumoniae Anaerobes Clostridium Fusobacterium fusiforme Propionibacterium acnes Other Bacteria Norcardiae Actinomyces Borrelia recurrentis Chlamydophila psittaci Chlamydia trachomatis Mycoplasma pneumoniae Rickettsiae Treponema pallidum Treponema pallidum pertenue Ureaplasma urealyticum Parasites Balantidium coli Entamoeba Plasmodium falciparum Doxycycline has been found to be active against the asexual erythrocytic forms of Plasmodium falciparum, but not against the gametocytes of P. The precise mechanism of action of the drug is not known. When available, the clinical microbiology laboratory should provide the results of in vitro 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). 1,2,4,6,7 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 For anaerobic bacteria, the susceptibility to doxycycline can be determined by a standardized test method 5 Table 1: Susceptibility Test Interpretive Criteria for Doxycycline and Tetracycline Bacteria 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 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 10-12 <= 9 - - - Tetracycline <= 4 8 >= 16 >= 15 12-14 <= 11 - - - Anaerobes Tetracycline - - - - - - <= 4 8 >= 16 Bacillus anthracis 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. Doxycycline <= 1 - - - - - - - - Tetracycline <= 1 - - - - - - - - Brucella Doxycycline <= 1 - - - - - - - - Tetracycline <= 1 - - - - - - - - Enterobacteriaceae Doxycycline <= 4 8 >= 16 >= 14 11-13 <= 10 - - - Tetracycline <= 4 8 >= 16 >= 15 12-14 <= 11 - - - Franciscella tularensis Doxycycline <= 4 - - - - - - - - Tetracycline <= 4 - - - - - - - - Haemophilus influenzae Tetracycline <= 2 4 >= 8 >= 29 26-28 <= 25 - - - Mycoplasma pneumoniae Tetracycline - - - - - - <= 2 - - Neisseria gonorrhoeae 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) Tetracycline - - - >=38 31-37 <=30 <=0. 5-1 >=2 Norcardiae Actinomyces Doxycycline <=1 2-4 >=8 - - - - - - Streptococcus pneumoniae Doxycycline <=0. 5 > 1 > 28 25-27 < 24 - - - Tetracycline < 1 2 > 4 > 28 25-27 < 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 Intermediate Resistant 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 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 - 8 - - Tetracycline 8 - 32 - - Escherichia coli ATCC 25922 Doxycycline 0. 5 en dash 2 18 - 24 - Tetracycline 0. 5 - 2 18 - 25 - Eggerthella lenta Doxycycline 2 en dash 16 - - Haemophilus influenzae ATCC 49247 Tetracycline 4 - 32 14 - 22 - Neisseria gonorrhoeae ATCC 49226 Tetracycline - 30 - 42 0. 25 - 1 Staphylococcus aureus ATCC 25923 Doxycycline - 23 - 29 - Tetracycline - 24 - 30 - Staphylococcus aureus ATCC 29213 Doxycycline 0. 5 - - Tetracycline 0. 12 - 1 - - Streptococcus pneumoniae ATCC 49619 Doxycycline 0. 015 en dash 0. 12 25 - 34 - Tetracycline 0. 06 en dash 0. 5 27 - 31 - Bacteroides fragilis ATCC 25285 Tetracycline - - 0. 12 en dash 0. 5 Bacteroides thetaiotaomicron ATCC 29741 Doxycycline 2 en dash 8 - - Tetracycline - - 8 en dash 32 Mycoplasma pneumoniae ATCC 29342 Tetracycline 0. 5 Ureaplasma urealyticum ATCC 33175 Tetracycline - - >=8.
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 Gram-Negative Bacteria Acinetobacter Bartonella bacilliformis Brucella Enterobacter aerogenes Escherichia coli Francisella tularensis Haemophilus ducreyi Haemophilus influenzae Klebsiella granulomatis Klebsiella Neisseria gonorrhoeae Shigella Vibrio cholerae Vibrio fetus Yersinia pestis Gram-Positive Bacteria Bacillus anthracis Streptococcus pneumoniae Anaerobes Clostridium Fusobacterium fusiforme Propionibacterium acnes Other Bacteria Norcardiae Actinomyces Borrelia recurrentis Chlamydophila psittaci Chlamydia trachomatis Mycoplasma pneumoniae Rickettsiae Treponema pallidum Treponema pallidum pertenue Ureaplasma urealyticum Parasites Balantidium coli Entamoeba Plasmodium falciparum Doxycycline has been found to be active against the asexual erythrocytic forms of Plasmodium falciparum, but not against the gametocytes of P. The precise mechanism of action of the drug is not known.
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). 1,2,4,6,7
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
ANIMAL PHARMACOLOGY AND ANIMAL TOXICOLOGY
Hyperpigmentation of the thyroid has been produced by members of the tetracycline class in the following species: in rats by oxytetracycline, doxycycline, tetracycline PO 4 4 Minocycline, tetracycline PO 4 Treatment of various animal species with this class of drugs has also resulted in the induction of thyroid hyperplasia in the following: in rats and dogs (minocycline); in chickens (chlortetracycline); and in rats and mice (oxytetracycline). Adrenal gland hyperplasia has been observed in goats and rats treated with oxytetracycline.">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. Following a 200 mg dose, normal adult volunteers averaged peak serum levels of 2. 6 mcg/mL of doxycycline at 2 hours, decreasing to 1. 45 mcg/mL at 24 hours. Excretion of doxycycline by the kidney is about 40%/72 hours in individuals with normal function (creatinine clearance about 75 mL/min. This percentage excretion may fall as low as 1 - 5%/72 hours in individuals with severe renal insufficiency (creatinine clearance below 10 mL/min. Studies have shown no significant difference in serum half-life of doxycycline (range 18-22 hours) in individuals with normal and severely impaired renal function. Hemodialysis does not alter serum half-life. Results of animal studies indicate that tetracyclines cross the placenta and are found in fetal tissues. 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 Gram-Negative Bacteria Acinetobacter Bartonella bacilliformis Brucella Enterobacter aerogenes Escherichia coli Francisella tularensis Haemophilus ducreyi Haemophilus influenzae Klebsiella granulomatis Klebsiella Neisseria gonorrhoeae Shigella Vibrio cholerae Vibrio fetus Yersinia pestis Gram-Positive Bacteria Bacillus anthracis Streptococcus pneumoniae Anaerobes Clostridium Fusobacterium fusiforme Propionibacterium acnes Other Bacteria Norcardiae Actinomyces Borrelia recurrentis Chlamydophila psittaci Chlamydia trachomatis Mycoplasma pneumoniae Rickettsiae Treponema pallidum Treponema pallidum pertenue Ureaplasma urealyticum Parasites Balantidium coli Entamoeba Plasmodium falciparum Doxycycline has been found to be active against the asexual erythrocytic forms of Plasmodium falciparum, but not against the gametocytes of P. The precise mechanism of action of the drug is not known. When available, the clinical microbiology laboratory should provide the results of in vitro 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). 1,2,4,6,7 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 For anaerobic bacteria, the susceptibility to doxycycline can be determined by a standardized test method 5 Table 1: Susceptibility Test Interpretive Criteria for Doxycycline and Tetracycline Bacteria 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 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 10-12 <= 9 - - - Tetracycline <= 4 8 >= 16 >= 15 12-14 <= 11 - - - Anaerobes Tetracycline - - - - - - <= 4 8 >= 16 Bacillus anthracis 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. Doxycycline <= 1 - - - - - - - - Tetracycline <= 1 - - - - - - - - Brucella Doxycycline <= 1 - - - - - - - - Tetracycline <= 1 - - - - - - - - Enterobacteriaceae Doxycycline <= 4 8 >= 16 >= 14 11-13 <= 10 - - - Tetracycline <= 4 8 >= 16 >= 15 12-14 <= 11 - - - Franciscella tularensis Doxycycline <= 4 - - - - - - - - Tetracycline <= 4 - - - - - - - - Haemophilus influenzae Tetracycline <= 2 4 >= 8 >= 29 26-28 <= 25 - - - Mycoplasma pneumoniae Tetracycline - - - - - - <= 2 - - Neisseria gonorrhoeae 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) Tetracycline - - - >=38 31-37 <=30 <=0. 5-1 >=2 Norcardiae Actinomyces Doxycycline <=1 2-4 >=8 - - - - - - Streptococcus pneumoniae Doxycycline <=0. 5 > 1 > 28 25-27 < 24 - - - Tetracycline < 1 2 > 4 > 28 25-27 < 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 Intermediate Resistant 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 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 - 8 - - Tetracycline 8 - 32 - - Escherichia coli ATCC 25922 Doxycycline 0. 5 en dash 2 18 - 24 - Tetracycline 0. 5 - 2 18 - 25 - Eggerthella lenta Doxycycline 2 en dash 16 - - Haemophilus influenzae ATCC 49247 Tetracycline 4 - 32 14 - 22 - Neisseria gonorrhoeae ATCC 49226 Tetracycline - 30 - 42 0. 25 - 1 Staphylococcus aureus ATCC 25923 Doxycycline - 23 - 29 - Tetracycline - 24 - 30 - Staphylococcus aureus ATCC 29213 Doxycycline 0. 5 - - Tetracycline 0. 12 - 1 - - Streptococcus pneumoniae ATCC 49619 Doxycycline 0. 015 en dash 0. 12 25 - 34 - Tetracycline 0. 06 en dash 0. 5 27 - 31 - Bacteroides fragilis ATCC 25285 Tetracycline - - 0. 12 en dash 0. 5 Bacteroides thetaiotaomicron ATCC 29741 Doxycycline 2 en dash 8 - - Tetracycline - - 8 en dash 32 Mycoplasma pneumoniae ATCC 29342 Tetracycline 0. 5 Ureaplasma urealyticum ATCC 33175 Tetracycline - - >=8.
Microbiology
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 Gram-Negative Bacteria Acinetobacter Bartonella bacilliformis Brucella Enterobacter aerogenes Escherichia coli Francisella tularensis Haemophilus ducreyi Haemophilus influenzae Klebsiella granulomatis Klebsiella Neisseria gonorrhoeae Shigella Vibrio cholerae Vibrio fetus Yersinia pestis Gram-Positive Bacteria Bacillus anthracis Streptococcus pneumoniae Anaerobes Clostridium Fusobacterium fusiforme Propionibacterium acnes Other Bacteria Norcardiae Actinomyces Borrelia recurrentis Chlamydophila psittaci Chlamydia trachomatis Mycoplasma pneumoniae Rickettsiae Treponema pallidum Treponema pallidum pertenue Ureaplasma urealyticum Parasites Balantidium coli Entamoeba Plasmodium falciparum Doxycycline has been found to be active against the asexual erythrocytic forms of Plasmodium falciparum, but not against the gametocytes of P. The precise mechanism of action of the drug is not known. When available, the clinical microbiology laboratory should provide the results of in vitro 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). 1,2,4,6,7 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 For anaerobic bacteria, the susceptibility to doxycycline can be determined by a standardized test method 5 Table 1: Susceptibility Test Interpretive Criteria for Doxycycline and Tetracycline Bacteria 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 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 10-12 <= 9 - - - Tetracycline <= 4 8 >= 16 >= 15 12-14 <= 11 - - - Anaerobes Tetracycline - - - - - - <= 4 8 >= 16 Bacillus anthracis 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. Doxycycline <= 1 - - - - - - - - Tetracycline <= 1 - - - - - - - - Brucella Doxycycline <= 1 - - - - - - - - Tetracycline <= 1 - - - - - - - - Enterobacteriaceae Doxycycline <= 4 8 >= 16 >= 14 11-13 <= 10 - - - Tetracycline <= 4 8 >= 16 >= 15 12-14 <= 11 - - - Franciscella tularensis Doxycycline <= 4 - - - - - - - - Tetracycline <= 4 - - - - - - - - Haemophilus influenzae Tetracycline <= 2 4 >= 8 >= 29 26-28 <= 25 - - - Mycoplasma pneumoniae Tetracycline - - - - - - <= 2 - - Neisseria gonorrhoeae 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) Tetracycline - - - >=38 31-37 <=30 <=0. 5-1 >=2 Norcardiae Actinomyces Doxycycline <=1 2-4 >=8 - - - - - - Streptococcus pneumoniae Doxycycline <=0. 5 > 1 > 28 25-27 < 24 - - - Tetracycline < 1 2 > 4 > 28 25-27 < 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 Intermediate Resistant 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 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 - 8 - - Tetracycline 8 - 32 - - Escherichia coli ATCC 25922 Doxycycline 0. 5 en dash 2 18 - 24 - Tetracycline 0. 5 - 2 18 - 25 - Eggerthella lenta Doxycycline 2 en dash 16 - - Haemophilus influenzae ATCC 49247 Tetracycline 4 - 32 14 - 22 - Neisseria gonorrhoeae ATCC 49226 Tetracycline - 30 - 42 0. 25 - 1 Staphylococcus aureus ATCC 25923 Doxycycline - 23 - 29 - Tetracycline - 24 - 30 - Staphylococcus aureus ATCC 29213 Doxycycline 0. 5 - - Tetracycline 0. 12 - 1 - - Streptococcus pneumoniae ATCC 49619 Doxycycline 0. 015 en dash 0. 12 25 - 34 - Tetracycline 0. 06 en dash 0. 5 27 - 31 - Bacteroides fragilis ATCC 25285 Tetracycline - - 0. 12 en dash 0. 5 Bacteroides thetaiotaomicron ATCC 29741 Doxycycline 2 en dash 8 - - Tetracycline - - 8 en dash 32 Mycoplasma pneumoniae ATCC 29342 Tetracycline 0. 5 Ureaplasma urealyticum ATCC 33175 Tetracycline - - >=8.
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 Gram-Negative Bacteria Acinetobacter Bartonella bacilliformis Brucella Enterobacter aerogenes Escherichia coli Francisella tularensis Haemophilus ducreyi Haemophilus influenzae Klebsiella granulomatis Klebsiella Neisseria gonorrhoeae Shigella Vibrio cholerae Vibrio fetus Yersinia pestis Gram-Positive Bacteria Bacillus anthracis Streptococcus pneumoniae Anaerobes Clostridium Fusobacterium fusiforme Propionibacterium acnes Other Bacteria Norcardiae Actinomyces Borrelia recurrentis Chlamydophila psittaci Chlamydia trachomatis Mycoplasma pneumoniae Rickettsiae Treponema pallidum Treponema pallidum pertenue Ureaplasma urealyticum Parasites Balantidium coli Entamoeba Plasmodium falciparum Doxycycline has been found to be active against the asexual erythrocytic forms of Plasmodium falciparum, but not against the gametocytes of P. The precise mechanism of action of the drug is not known.
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). 1,2,4,6,7
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
ANIMAL PHARMACOLOGY AND ANIMAL TOXICOLOGY
Hyperpigmentation of the thyroid has been produced by members of the tetracycline class in the following species: in rats by oxytetracycline, doxycycline, tetracycline PO 4 4 Minocycline, tetracycline PO 4 Treatment of various animal species with this class of drugs has also resulted in the induction of thyroid hyperplasia in the following: in rats and dogs (minocycline); in chickens (chlortetracycline); and in rats and mice (oxytetracycline). Adrenal gland hyperplasia has been observed in goats and rats treated with oxytetracycline.

INDICATIONS AND USAGE
To reduce the development of drug-resistant bacteria and maintain effectiveness of Doxycycline Hyclate Capsules & Doxycycline Hyclate Tablets and other antibacterial drugs, Doxycycline Hyclate Capsules & Doxycycline Hyclate Tablets should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. 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 Chlamydophila psittaci Trachoma caused by Chlamydia trachomatis, 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 Bartonellosis due to Bartonella bacilliformis Granuloma inguinale caused by Klebsiella 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 bacteria, when bacteriologic testing indicates appropriate susceptibility to the drug: Escherichia coli. Enterobacter aerogenes Shigella Acinetobacter Respiratory tract infections caused by Haemophilus influenzae Respiratory tract and urinary tract infections caused by Klebsiella 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, 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 pallidum pertenue Listeriosis due to Listeria monocytogenes Vincent''s infection caused by Fusobacterium fusiforme Actinomycosis caused by Actinomyces israelii Infections caused by Clostridium In acute intestinal amebiasis, doxycycline may be a useful adjunct to amebicides. In severe acne, doxycycline may be useful adjunctive therapy. Doxycycline is indicated for the prophylaxis of malaria due to Plasmodium falciparum DOSAGE AND ADMINISTRATION Information for Patients.
Prophylaxis
Doxycycline is indicated for the prophylaxis of malaria due to Plasmodium falciparum DOSAGE AND ADMINISTRATION Information for Patients

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 doxycycline is 200 mg on the first day of treatment (administered 100 mg every 12 hours) followed by a maintenance dose of 100 mg/day. In the management of more severe infections (particularly chronic infections of the urinary tract), 100 mg every 12 hours is recommended. For children above eight years of age: The recommended dosage schedule for children weighing 100 pounds or less is 2 mg/lb of body weight divided into two doses on the first day of treatment, followed by 1mg/lb of body weight given as a single daily dose or divided into two doses, on subsequent days. For more severe infections, up to 2 mg/lb of body weight may be used. For children over 100 lb the usual adult dose should be used. The therapeutic antibacterial serum activity will usually persist for 24 hours following recommended dosage. 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, it is recommended that doxycycline be given with food or milk. The absorption of doxycycline is not markedly influenced by simultaneous ingestion of food or milk. Studies to date have indicated that administration of doxycycline at the usual recommended doses does not lead to excessive accumulation of doxycycline in patients with renal impairment. 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. The dose may be administered with food, including milk or carbonated beverage, as required. Uncomplicated urethral, endocervical, or rectal infection in adults caused by Chlamydia trachomatis Nongonococcal urethritis (NGU) caused by C. trachomatis U. urealyticum Syphilis - early: Patients who are allergic to penicillin should be treated with doxycycline 100 mg, by mouth, twice a day for 2 weeks. Syphilis of more than one year's duration: Patients who are allergic to penicillin should be treated with doxycycline 100 mg, by mouth, twice a day for 4 weeks. Acute epididymo-orchitis caused by N. gonorrhoeae Acute epididymo-orchitis caused by C. trachomatis For prophylaxis of malaria: For adults, the recommended dose is 100 mg daily. For children over 8 years of age, the recommended dose is 2 mg/kg given once daily up to the adult dose. Prophylaxis should begin 1-2 days before travel to the malarious area. Prophylaxis should be continued daily during travel in the malarious area and for 4 weeks after the traveler leaves the malarious area. Inhalational anthrax (post-exposure): ADULTS: 100 mg of doxycycline, by mouth, twice a day for 60 days. CHILDREN: weighing less than 100 lb (45 kg); 1 mg/lb (2.2 mg/kg) of body weight by mouth, twice a day for 60 days. Children weighing 100 lb or more should receive the adult dose.

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. (See DOSAGE AND ADMINISTRATION Skin: toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, maculopapular and erythematous rashes. Exfoliative dermatitis has been reported but is uncommon. Photosensitivity is discussed above. (See WARNINGS Renal toxicity: Rise in BUN has been reported and is apparently dose related. (See WARNINGS Immune: Hypersensitivity reactions including urticaria, angioneurotic edema, anaphylaxis, anaphylactoid purpura, serum sickness, pericarditis, exacerbation of systemic lupus erythematosus, and drug rash with eosinophilia and systemic symptoms (DRESS). Blood: Hemolytic anemia, thrombocytopenia, neutropenia, and eosinophilia have been reported. Other: bulging fontanels in infants and intracranial hypertension in adults. (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 studies are known to occur. To report suspected ADVERSE REACTIONS, contact HARRIS Pharmaceutical at 1-800-983-4708 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

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

Pregnancy
There are no adequate and well-controlled studies on the use of doxycycline in pregnant women. The vast majority of reported experience with doxycycline during human pregnancy is short-term, first trimester exposure. There are no human data available to assess the effects of long-term therapy of doxycycline in pregnant women, such as that proposed for treatment of anthrax exposure. An expert review of published data on experiences with doxycycline use during pregnancy by TERIS -the Teratogen Information System -concluded that therapeutic doses during pregnancy are unlikely to pose a substantial teratogenic risk (the quantity and quality of data were assessed as limited to fair), but the data are insufficient to state that there is no risk a b A small prospective study of 81 pregnancies describes 43 pregnant women treated for 10 days with doxycycline during early first trimester. All mothers reported their exposed infants were normal at 1 year of age c (See WARNINGS.
Nonteratogenic Effects
(See WARNINGS
Nursing Mothers
Tetracyclines are excreted in human milk; however, the extent of absorption of tetracyclines, including doxycycline, by the breastfed infant is not known. Short-term use by lactating women is not necessarily contraindicated; however, the effects of prolonged exposure to doxycycline in breast milk are unknown d WARNINGS
Pediatric Use
See WARNINGS DOSAGE AND ADMINISTRATION

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. Absorption of tetracyclines is impaired by antacids containing aluminum, calcium, or magnesium, and iron-containing preparations. Absorption of tetracyclines is impaired by bismuth subsalicylate. Barbiturates, carbamazepine, and phenytoin decrease the half-life of doxycycline. The concurrent use of tetracycline and Penthrane registered Concurrent use of tetracycline may render oral contraceptives less effective.
Drug/Laboratory Test Interactions
False elevations of urinary catecholamine levels may occur due to interference with the fluorescence test.

= 16 >= 14 11-13 <= 10 - - - Tetracycline <= 4 8 >= 16 >= 15 12-14 <= 11 - - - Franciscella tularensis Doxycycline <= 4 - - - - - - - - Tetracycline <= 4 - - - - - - - - Haemophilus influenzae Tetracycline <= 2 4 >= 8 >= 29 26-28 <= 25 - - - Mycoplasma pneumoniae Tetracycline - - - - - - <= 2 - - Neisseria gonorrhoeae 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) Tetracycline - - - >=38 31-37 <=30 <=0. 5-1 >=2 Norcardiae Actinomyces Doxycycline <=1 2-4 >=8 - - - - - - Streptococcus pneumoniae Doxycycline <=0. 5 > 1 > 28 25-27 < 24 - - - Tetracycline < 1 2 > 4 > 28 25-27 < 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 Intermediate Resistant 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 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 - 8 - - Tetracycline 8 - 32 - - Escherichia coli ATCC 25922 Doxycycline 0. 5 en dash 2 18 - 24 - Tetracycline 0. 5 - 2 18 - 25 - Eggerthella lenta Doxycycline 2 en dash 16 - - Haemophilus influenzae ATCC 49247 Tetracycline 4 - 32 14 - 22 - Neisseria gonorrhoeae ATCC 49226 Tetracycline - 30 - 42 0. 25 - 1 Staphylococcus aureus ATCC 25923 Doxycycline - 23 - 29 - Tetracycline - 24 - 30 - Staphylococcus aureus ATCC 29213 Doxycycline 0. 5 - - Tetracycline 0. 12 - 1 - - Streptococcus pneumoniae ATCC 49619 Doxycycline 0. 015 en dash 0. 12 25 - 34 - Tetracycline 0. 06 en dash 0. 5 27 - 31 - Bacteroides fragilis ATCC 25285 Tetracycline - - 0. 12 en dash 0. 5 Bacteroides thetaiotaomicron ATCC 29741 Doxycycline 2 en dash 8 - - Tetracycline - - 8 en dash 32 Mycoplasma pneumoniae ATCC 29342 Tetracycline 0. 5 Ureaplasma urealyticum ATCC 33175 Tetracycline - - >=8.
Anaerobic Techniques
For anaerobic bacteria, the susceptibility to doxycycline can be determined by a standardized test method 5 Table 1: Susceptibility Test Interpretive Criteria for Doxycycline and Tetracycline Bacteria 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 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 10-12 <= 9 - - - Tetracycline <= 4 8 >= 16 >= 15 12-14 <= 11 - - - Anaerobes Tetracycline - - - - - - <= 4 8 >= 16 Bacillus anthracis 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. Doxycycline <= 1 - - - - - - - - Tetracycline <= 1 - - - - - - - - Brucella Doxycycline <= 1 - - - - - - - - Tetracycline <= 1 - - - - - - - - Enterobacteriaceae Doxycycline <= 4 8 >= 16 >= 14 11-13 <= 10 - - - Tetracycline <= 4 8 >= 16 >= 15 12-14 <= 11 - - - Franciscella tularensis Doxycycline <= 4 - - - - - - - - Tetracycline <= 4 - - - - - - - - Haemophilus influenzae Tetracycline <= 2 4 >= 8 >= 29 26-28 <= 25 - - - Mycoplasma pneumoniae Tetracycline - - - - - - <= 2 - - Neisseria gonorrhoeae 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) Tetracycline - - - >=38 31-37 <=30 <=0.25 0.5-1 >=2 Norcardiae Actinomyces Doxycycline <=1 2-4 >=8 - - - - - - Streptococcus pneumoniae Doxycycline <=0.25 0.5 > 1 > 28 25-27 < 24 - - - Tetracycline < 1 2 > 4 > 28 25-27 < 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 Intermediate Resistant
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 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 - 8 - - Tetracycline 8 - 32 - - Escherichia coli ATCC 25922 Doxycycline 0.5 en dash 2 18 - 24 - Tetracycline 0.5 - 2 18 - 25 - Eggerthella lenta Doxycycline 2 en dash 16 - - Haemophilus influenzae ATCC 49247 Tetracycline 4 - 32 14 - 22 - Neisseria gonorrhoeae ATCC 49226 Tetracycline - 30 - 42 0.25 - 1 Staphylococcus aureus ATCC 25923 Doxycycline - 23 - 29 - Tetracycline - 24 - 30 - Staphylococcus aureus ATCC 29213 Doxycycline 0.12 - 0.5 - - Tetracycline 0.12 - 1 - - Streptococcus pneumoniae ATCC 49619 Doxycycline 0.015 en dash 0.12 25 - 34 - Tetracycline 0.06 en dash 0.5 27 - 31 - Bacteroides fragilis ATCC 25285 Tetracycline - - 0.12 en dash 0.5 Bacteroides thetaiotaomicron ATCC 29741 Doxycycline 2 en dash 8 - - Tetracycline - - 8 en dash 32 Mycoplasma pneumoniae ATCC 29342 Tetracycline 0.06-0.5 - 0.06-0.5 Ureaplasma urealyticum ATCC 33175 Tetracycline - - >=8
Treatment
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 Chlamydophila psittaci Trachoma caused by Chlamydia trachomatis, 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 Bartonellosis due to Bartonella bacilliformis Granuloma inguinale caused by Klebsiella 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 bacteria, when bacteriologic testing indicates appropriate susceptibility to the drug: Escherichia coli. Enterobacter aerogenes Shigella Acinetobacter Respiratory tract infections caused by Haemophilus influenzae Respiratory tract and urinary tract infections caused by Klebsiella 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, 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 pallidum pertenue Listeriosis due to Listeria monocytogenes Vincent''s infection caused by Fusobacterium fusiforme Actinomycosis caused by Actinomyces israelii Infections caused by Clostridium In acute intestinal amebiasis, doxycycline may be a useful adjunct to amebicides. In severe acne, doxycycline may be useful adjunctive therapy.
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-GRAY-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, EXCEPT FOR ANTHRAX, INCLUDING INHALATIONAL ANTHRAX (POST-EXPOSURE), UNLESS OTHER DRUGS ARE NOT LIKELY TO BE EFFECTIVE OR ARE CONTRAINDICATED. Clostridium difficile C. difficile C. difficile C. difficile If CDAD is suspected or confirmed, ongoing use of antibacterial drugs not directed against C. difficile C. difficile, Intracranial hypertension (IH, pseudotumor cerebri) has been associated with the use of tetracyclines including Doxycycline Hyclate Capsules and Doxycycline Hyclate Capsules. 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 Hyclate Capsules and Doxycycline Hyclate Capsules 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. All tetracyclines form a stable calcium complex in any bone-forming tissue. A decrease in fibula growth rate has been observed in prematures given oral tetracycline in doses of 25 mg/kg every 6 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 embryotoxicity has also been noted in animals treated early in pregnancy. If any tetracycline is used during pregnancy or if the patient becomes pregnant while taking this drug, 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.
Carcinogenesis,Mutagenesis, Impairment Of Fertility
Long-term studies in animals to evaluate carcinogenic potential of doxycycline have not been conducted. However, there has been evidence of oncogenic activity in rats in studies with the related antibacterial drugs, oxytetracycline (adrenal and pituitary tumors), and minocycline (thyroid tumors). Likewise, although mutagenicity studies of doxycycline have not been conducted, positive results in in vitro Doxycycline administered orally at dosage levels as high as 250 mg/kg/day had no apparent effect on the fertility of female rats. Effect on male fertility has not been studied.
Teratogenic Effects
There are no adequate and well-controlled studies on the use of doxycycline in pregnant women. The vast majority of reported experience with doxycycline during human pregnancy is short-term, first trimester exposure. There are no human data available to assess the effects of long-term therapy of doxycycline in pregnant women, such as that proposed for treatment of anthrax exposure. An expert review of published data on experiences with doxycycline use during pregnancy by TERIS -the Teratogen Information System -concluded that therapeutic doses during pregnancy are unlikely to pose a substantial teratogenic risk (the quantity and quality of data were assessed as limited to fair), but the data are insufficient to state that there is no risk a b A small prospective study of 81 pregnancies describes 43 pregnant women treated for 10 days with doxycycline during early first trimester. All mothers reported their exposed infants were normal at 1 year of age c
Labor and Delivery
The effect of tetracyclines on labor and delivery is unknown.
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.
REFERENCES
Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing; Twenty-fifth Informational Supplement, Clinical and Laboratory Standards Institute. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard - 10 th Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Disk Susceptibility Tests; Approved Standard - 11 th Clinical and Laboratory Standards Institute. Methods for Antimicrobial Dilution and Disk Susceptibility Testing of Infrequently Isolated or Fastidious Bacteria; Approved Guideline em dashSecond Edition. Clinical and Laboratory Standards Institute (CLSI). Methods for Antimicrobial Susceptibility Testing of Anaerobic Bacteria; Approved Standard - Eighth Edition. Clinical and Laboratory Standards Institute. Susceptibility Testing of Mycobacteria, Nocardiae, and Other Aerobic Actinomycetes; Approved Standardem dashSecond Edition Clinical and Laboratory Standards Institute. Methods for Antimicrobial Susceptibility Testing for Human Mycoplasmas; Approved Guideline. Friedman JM and Polifka JE. Teratogenic Effects of Drugs. A Resource for Clinicians (TERIS) Cziezel AE and Rockenbauer M. Teratogenic study of doxycycline. Obstet Gynecol Horne HW Jr and Kundsin RB. The role of mycoplasma among 81 consecutive pregnancies: a prospective study. Int J Fertil Hale T. Medications and Mothers Milk.">Susceptibility Testing Methods
When available, the clinical microbiology laboratory should provide the results of in vitro 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). 1,2,4,6,7 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 For anaerobic bacteria, the susceptibility to doxycycline can be determined by a standardized test method 5 Table 1: Susceptibility Test Interpretive Criteria for Doxycycline and Tetracycline Bacteria 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 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 10-12 <= 9 - - - Tetracycline <= 4 8 >= 16 >= 15 12-14 <= 11 - - - Anaerobes Tetracycline - - - - - - <= 4 8 >= 16 Bacillus anthracis 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. Doxycycline <= 1 - - - - - - - - Tetracycline <= 1 - - - - - - - - Brucella Doxycycline <= 1 - - - - - - - - Tetracycline <= 1 - - - - - - - - Enterobacteriaceae Doxycycline <= 4 8 >= 16 >= 14 11-13 <= 10 - - - Tetracycline <= 4 8 >= 16 >= 15 12-14 <= 11 - - - Franciscella tularensis Doxycycline <= 4 - - - - - - - - Tetracycline <= 4 - - - - - - - - Haemophilus influenzae Tetracycline <= 2 4 >= 8 >= 29 26-28 <= 25 - - - Mycoplasma pneumoniae Tetracycline - - - - - - <= 2 - - Neisseria gonorrhoeae 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) Tetracycline - - - >=38 31-37 <=30 <=0. 5-1 >=2 Norcardiae Actinomyces Doxycycline <=1 2-4 >=8 - - - - - - Streptococcus pneumoniae Doxycycline <=0. 5 > 1 > 28 25-27 < 24 - - - Tetracycline < 1 2 > 4 > 28 25-27 < 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 Intermediate Resistant 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 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 - 8 - - Tetracycline 8 - 32 - - Escherichia coli ATCC 25922 Doxycycline 0. 5 en dash 2 18 - 24 - Tetracycline 0. 5 - 2 18 - 25 - Eggerthella lenta Doxycycline 2 en dash 16 - - Haemophilus influenzae ATCC 49247 Tetracycline 4 - 32 14 - 22 - Neisseria gonorrhoeae ATCC 49226 Tetracycline - 30 - 42 0. 25 - 1 Staphylococcus aureus ATCC 25923 Doxycycline - 23 - 29 - Tetracycline - 24 - 30 - Staphylococcus aureus ATCC 29213 Doxycycline 0. 5 - - Tetracycline 0. 12 - 1 - - Streptococcus pneumoniae ATCC 49619 Doxycycline 0. 015 en dash 0. 12 25 - 34 - Tetracycline 0. 06 en dash 0. 5 27 - 31 - Bacteroides fragilis ATCC 25285 Tetracycline - - 0. 12 en dash 0. 5 Bacteroides thetaiotaomicron ATCC 29741 Doxycycline 2 en dash 8 - - Tetracycline - - 8 en dash 32 Mycoplasma pneumoniae ATCC 29342 Tetracycline 0. 5 Ureaplasma urealyticum ATCC 33175 Tetracycline - - >=8.
Anaerobic Techniques
For anaerobic bacteria, the susceptibility to doxycycline can be determined by a standardized test method 5 Table 1: Susceptibility Test Interpretive Criteria for Doxycycline and Tetracycline Bacteria 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 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 10-12 <= 9 - - - Tetracycline <= 4 8 >= 16 >= 15 12-14 <= 11 - - - Anaerobes Tetracycline - - - - - - <= 4 8 >= 16 Bacillus anthracis 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. Doxycycline <= 1 - - - - - - - - Tetracycline <= 1 - - - - - - - - Brucella Doxycycline <= 1 - - - - - - - - Tetracycline <= 1 - - - - - - - - Enterobacteriaceae Doxycycline <= 4 8 >= 16 >= 14 11-13 <= 10 - - - Tetracycline <= 4 8 >= 16 >= 15 12-14 <= 11 - - - Franciscella tularensis Doxycycline <= 4 - - - - - - - - Tetracycline <= 4 - - - - - - - - Haemophilus influenzae Tetracycline <= 2 4 >= 8 >= 29 26-28 <= 25 - - - Mycoplasma pneumoniae Tetracycline - - - - - - <= 2 - - Neisseria gonorrhoeae 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) Tetracycline - - - >=38 31-37 <=30 <=0.25 0.5-1 >=2 Norcardiae Actinomyces Doxycycline <=1 2-4 >=8 - - - - - - Streptococcus pneumoniae Doxycycline <=0.25 0.5 > 1 > 28 25-27 < 24 - - - Tetracycline < 1 2 > 4 > 28 25-27 < 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 Intermediate Resistant
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 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 - 8 - - Tetracycline 8 - 32 - - Escherichia coli ATCC 25922 Doxycycline 0.5 en dash 2 18 - 24 - Tetracycline 0.5 - 2 18 - 25 - Eggerthella lenta Doxycycline 2 en dash 16 - - Haemophilus influenzae ATCC 49247 Tetracycline 4 - 32 14 - 22 - Neisseria gonorrhoeae ATCC 49226 Tetracycline - 30 - 42 0.25 - 1 Staphylococcus aureus ATCC 25923 Doxycycline - 23 - 29 - Tetracycline - 24 - 30 - Staphylococcus aureus ATCC 29213 Doxycycline 0.12 - 0.5 - - Tetracycline 0.12 - 1 - - Streptococcus pneumoniae ATCC 49619 Doxycycline 0.015 en dash 0.12 25 - 34 - Tetracycline 0.06 en dash 0.5 27 - 31 - Bacteroides fragilis ATCC 25285 Tetracycline - - 0.12 en dash 0.5 Bacteroides thetaiotaomicron ATCC 29741 Doxycycline 2 en dash 8 - - Tetracycline - - 8 en dash 32 Mycoplasma pneumoniae ATCC 29342 Tetracycline 0.06-0.5 - 0.06-0.5 Ureaplasma urealyticum ATCC 33175 Tetracycline - - >=8
Treatment
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 Chlamydophila psittaci Trachoma caused by Chlamydia trachomatis, 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 Bartonellosis due to Bartonella bacilliformis Granuloma inguinale caused by Klebsiella 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 bacteria, when bacteriologic testing indicates appropriate susceptibility to the drug: Escherichia coli. Enterobacter aerogenes Shigella Acinetobacter Respiratory tract infections caused by Haemophilus influenzae Respiratory tract and urinary tract infections caused by Klebsiella 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, 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 pallidum pertenue Listeriosis due to Listeria monocytogenes Vincent''s infection caused by Fusobacterium fusiforme Actinomycosis caused by Actinomyces israelii Infections caused by Clostridium In acute intestinal amebiasis, doxycycline may be a useful adjunct to amebicides. In severe acne, doxycycline may be useful adjunctive therapy.
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-GRAY-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, EXCEPT FOR ANTHRAX, INCLUDING INHALATIONAL ANTHRAX (POST-EXPOSURE), UNLESS OTHER DRUGS ARE NOT LIKELY TO BE EFFECTIVE OR ARE CONTRAINDICATED. Clostridium difficile C. difficile C. difficile C. difficile If CDAD is suspected or confirmed, ongoing use of antibacterial drugs not directed against C. difficile C. difficile, Intracranial hypertension (IH, pseudotumor cerebri) has been associated with the use of tetracyclines including Doxycycline Hyclate Capsules and Doxycycline Hyclate Capsules. 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 Hyclate Capsules and Doxycycline Hyclate Capsules 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. All tetracyclines form a stable calcium complex in any bone-forming tissue. A decrease in fibula growth rate has been observed in prematures given oral tetracycline in doses of 25 mg/kg every 6 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 embryotoxicity has also been noted in animals treated early in pregnancy. If any tetracycline is used during pregnancy or if the patient becomes pregnant while taking this drug, 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.
Carcinogenesis,Mutagenesis, Impairment Of Fertility
Long-term studies in animals to evaluate carcinogenic potential of doxycycline have not been conducted. However, there has been evidence of oncogenic activity in rats in studies with the related antibacterial drugs, oxytetracycline (adrenal and pituitary tumors), and minocycline (thyroid tumors). Likewise, although mutagenicity studies of doxycycline have not been conducted, positive results in in vitro Doxycycline administered orally at dosage levels as high as 250 mg/kg/day had no apparent effect on the fertility of female rats. Effect on male fertility has not been studied.
Teratogenic Effects
There are no adequate and well-controlled studies on the use of doxycycline in pregnant women. The vast majority of reported experience with doxycycline during human pregnancy is short-term, first trimester exposure. There are no human data available to assess the effects of long-term therapy of doxycycline in pregnant women, such as that proposed for treatment of anthrax exposure. An expert review of published data on experiences with doxycycline use during pregnancy by TERIS -the Teratogen Information System -concluded that therapeutic doses during pregnancy are unlikely to pose a substantial teratogenic risk (the quantity and quality of data were assessed as limited to fair), but the data are insufficient to state that there is no risk a b A small prospective study of 81 pregnancies describes 43 pregnant women treated for 10 days with doxycycline during early first trimester. All mothers reported their exposed infants were normal at 1 year of age c
Labor and Delivery
The effect of tetracyclines on labor and delivery is unknown.
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.
REFERENCES
Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing; Twenty-fifth Informational Supplement, Clinical and Laboratory Standards Institute. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard - 10 th Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Disk Susceptibility Tests; Approved Standard - 11 th Clinical and Laboratory Standards Institute. Methods for Antimicrobial Dilution and Disk Susceptibility Testing of Infrequently Isolated or Fastidious Bacteria; Approved Guideline em dashSecond Edition. Clinical and Laboratory Standards Institute (CLSI). Methods for Antimicrobial Susceptibility Testing of Anaerobic Bacteria; Approved Standard - Eighth Edition. Clinical and Laboratory Standards Institute. Susceptibility Testing of Mycobacteria, Nocardiae, and Other Aerobic Actinomycetes; Approved Standardem dashSecond Edition Clinical and Laboratory Standards Institute. Methods for Antimicrobial Susceptibility Testing for Human Mycoplasmas; Approved Guideline. Friedman JM and Polifka JE. Teratogenic Effects of Drugs. A Resource for Clinicians (TERIS) Cziezel AE and Rockenbauer M. Teratogenic study of doxycycline. Obstet Gynecol Horne HW Jr and Kundsin RB. The role of mycoplasma among 81 consecutive pregnancies: a prospective study. Int J Fertil Hale T. Medications and Mothers Milk.

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