DOXYCYCLINE- doxycycline capsule
Novel Laboratories, Inc.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of doxycycline capsules and other antibacterial drugs, doxycycline capsules should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.
Doxycycline is a broad-spectrum antibacterial synthetically derived from oxytetracycline. Doxycycline capsules USP, 50 mg, 75 mg, and 100 mg contain doxycycline monohydrate equivalent to 50 mg, 75 mg, and 100 mg of doxycycline for oral administration. The chemical designation of the light yellow to pale yellow powder is 2-Naphthacenecarboxamide,4-(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-,[4S -(4α,4aα,5α,5aα,6α,12aα)]-,monohydrate.
Doxycycline has a high degree of lipid solubility and a low affinity for calcium binding. It is highly stable in normal human serum. Doxycycline will not degrade into an epianhydro form.
Inert ingredients: colloidal silicon dioxide; magnesium stearate; microcrystalline cellulose; sodium starch glycolate; and a hard gelatin capsule which contains titanium dioxide, FD&C Red # 3, D&C Yellow # 10, gelatin, sodium lauryl sulfate, for the 50 mg strength; iron oxide black, iron oxide red, iron oxide yellow, titanium dioxide, gelatin, sodium lauryl sulfate for the 75 mg strength and iron oxide black, Iron Oxide Red, Iron Oxide Yellow, Titanium Dioxide, FD & C Red# 3, D&C Yellow # 10, gelatin, sodium lauryl sulfate for the 100 mg strength. The capsules are printed with edible ink containing shellac, titanium dioxide, black iron oxide, brown iron oxide and potassium hydroxide for 50 mg, 75 mg and 100 mg strengths.
Tetracyclines are readily absorbed and are bound to plasma proteins in varying degrees. They are concentrated by the liver in the bile and excreted in the urine and feces at high concentrations in a biologically active form. Doxycycline is virtually completely absorbed after oral administration.
Following a 200 mg dose of doxycycline monohydrate, 24 normal adult volunteers averaged the following serum concentration values:
|Average Observed Values Maximum Concentration||3.61 mcg/mL (± 0.9 sd)|
|Time of Maximum Concentration||2.60 hr (± 1.10 sd)|
|Elimination Rate Constant||0.049 per hr (± 0.030 sd)|
|Half-Life||16.33 hr (± 4.53 sd)|
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 to 22 hours) in individuals with normal and severely impaired renal function.
Hemodialysis does not alter serum half-life.
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.
Norcardiae and other aerobic Actinomyces species
Treponema pallidum subspecies pertenue
*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.
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 The MIC values should be interpreted according to the criteria provided in Table 1.
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.
For anaerobic bacteria, the susceptibility to doxycycline can be determined by a standardized test method5. The MIC values obtained should be interpreted according to the criteria provided in Table 1.
|Bacteria *||Minimal Inhibitory Concentration ( mcg per mL )||Zone Diameter ( mm )||Agar Dilution ( mcg per mL )|
|Acinetobacter spp .|
|Bacillus anthracis †|
|Brucella species †|
|Franciscella tularensis †|
|Tetracycline||≤2||4||≥8||≥29||26 to 28||≤25||–||–||–|
|Mycoplasma pneumoniae †|
|Neisseria gonorrhoeae ‡|
|Tetracycline||–||–||–||≥38||31 to 37||≤30||≤0.25||0.5 to 1||≥2|
|Norcardiae and other aerobicActinomyces species|
|Doxycycline||≤1||2 to 4||≥8||–||–||–||–||–||–|
|Doxycycline||≤0.25||0.5||>1||>28||25 to 27||<24||–||–||–|
|Tetracycline||<1||2||>4||>28||25 to 27||<24||–||–||–|
|* Organisms susceptible to tetracycline are also considered susceptible to doxycycline. However, some organisms that are intermediate or resistant toTetracycline 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, theyshould 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 ≥ to 16 mcg / mL).|
A report of Susceptible (S) indicates that 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.
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 test1,2,3,4,5,6,7. 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.
|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|
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