Demeclocycline Hydrochloride: Package Insert and Label Information
DEMECLOCYCLINE HYDROCHLORIDE — demeclocycline hydrochloride tablet
Carilion Materials Management
Full Prescribing Information
To reduce the development of drug-resistant bacteria and maintain the effectiveness of demeclocycline hydrochloride tablets and other antibacterial drugs, demeclocycline hydrochloride tablets should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.
DESCRIPTION
Demeclocycline hydrochloride is an antibiotic isolated from a mutant strain of . Chemically it is 7-Chloro-4-(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,6,10,12, 12a-pentahydroxy-1,11-dioxo-2-naphthacenecarboxamide monohydrochloride. Its structural formula is: Streptomyces aureofaciens
Demeclocycline hydrochloride film coated tablets for oral administration contain 150 mg or 300 mg of demeclocycline hydrochloride and the following inactive ingredients: alginic acid, corn starch, ethylcellulose, FD&C Red 40 aluminum lake, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polyvinyl alcohol, sodium lauryl sulfate, talc and titanium dioxide. In addition, the 150 mg tablet contains D&C Red 27 aluminum lake.
CLINICAL PHARMACOLOGY
The absorption of demeclocycline is slower than that of tetracycline. The time to reach the peak concentration is about 4 hours. After a 150 mg oral dose of demeclocycline tablet, the mean concentrations at 1 hour and 3 hours are 0.46 and 1.22 mcg/mL (n = 6), respectively. The serum half-life ranges between 10 and 16 hours.
Pharmacokinetics
When demeclocycline hydrochloride is given concomitantly with some dairy products, or antacids containing aluminum, calcium, or magnesium, the extent of absorption is reduced by more than 50%.
Demeclocycline hydrochloride penetrates well into various body fluids and tissues. The percent of demeclocycline hydrochloride bound to plasma protein is about 40% using a dialysis equilibrium method and 90% using an ultra-filtration method. Demeclocycline hydrochloride, like other tetracyclines, is concentrated in the liver and excreted into the bile where it is found in much higher concentrations than in the blood. The rate of demeclocycline hydrochloride renal clearance (35 mL/min/1.73 m ) is less than half that of tetracycline. Following a single 150 mg dose of demeclocycline hydrochloride in normal volunteers, 44% (n = 8) was excreted in urine and 13% and 46%, respectively, were excreted in feces in two patients within 96 hours as active drug. 2
The tetracyclines are primarily bacteriostatic and are thought to exert their antimicrobial effect by the inhibition of protein synthesis. The tetracyclines, including demeclocycline, have a similar antimicrobial spectrum of activity against a wide range of gram-negative and gram-positive organisms. Cross-resistance of these organisms to tetracyclines is common. Microbiology
Demeclocycline has been shown to be active against most strains of the following microorganisms, both and in clinical infections as described in the section. in vitro INDICATIONS AND USAGE
| AEROBIC GRAM-POSITIVE MICROORGANISMS: | |
| Bacillus anthracis | Listeria monocytogenes |
| Staphylococcus aureus | Streptococcus pneumoniae |
| AEROBIC GRAM-NEGATIVE MICROORGANISMS: | |
| Bartonella bacilliformis | species Brucella |
| Calymmatobacterium granulomatis | Campylobacter fetus |
| Francisella tularensis | Haemophilus ducreyi |
| Haemophilus influenzae | Neisseria gonorrhoeae |
| Vibrio cholerae | Yersinia pestis |
Because many strains of the following groups of gram-negative microorganisms have been shown to be resistant to tetracyclines, culture and susceptibility testing are especially recommended:
| species Acinetobacter | Enterobacter aerogenes |
| Escherichia coli | species Klebsiella |
| Shigella species | |
| OTHER MICROORGANISMS: | |
| Actinomyces israelii | Borrelia recurrentis |
| Chlamydia psittaci | Chlamydia trachomatis |
| species Clostridium | species Entamoeba |
| Fusobacterium fusiforme | Mycoplasma pneumoniae |
| Propionibacterium acnes | Rickettsiae |
| subspecies Treponema pallidum pallidum | subspecies Treponema pallidum pertenue |
| Ureaplasma urealyticum | |
Susceptibility Tests
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 procedure. Standardized procedures are based on a dilution method (broth or agar) or equivalent with standardized inoculum concentrations and standardized concentrations of demeclocycline hydrochloride or tetracycline powder. The MIC values should be interpreted according to the following criteria: 1
For organisms other than species, and species: Haemophilus Neisseria gonorrhoeae Streptococcus 2
| MIC (mcg/mL) | Interpretation |
| ≤ 4 | Susceptible (S) |
| 8 | Intermediate (I) |
| ≥16 | Resistant (R) |
For and species: Haemophilus Streptococcus 2
| MIC (mcg/mL) | Interpretation |
| ≤ 2 | Susceptible (S) |
| 4 | Intermediate (I) |
| ≥8 | Resistant (R) |
For : Neisseria gonorrhoeae 2
| MIC (mcg/mL) | Interpretation |
| ≤ 0.25 | Susceptible (S) |
| 0.5 to 1 | Intermediate (I) |
| ≥2 | Resistant (R) |
A report of “Susceptible” indicates that the pathogen is likely to be inhibited by usually achievable concentrations of the antimicrobial compound in blood. A report of “Intermediate” indicates that the result should be considered equivocal, and, if the microorganism 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 is physiologically concentrated or in situations where high dosage of drug can be used. This category also provides a buffer zone which prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of “Resistant” indicates that usually achievable concentrations of the antimicrobial compound in the blood are unlikely to be inhibitory and that other therapy should be selected.
Standardized susceptibility test procedures require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures. Standard demeclocycline or tetracycline powder should provide the following MIC values: 2
| Microorganism | MIC (mcg/mL) | Microorganism | MIC (mcg/mL) |
| ATCC 25922 E.coli, | 1 to 4 | ATCC 49226 N. gonorrhoeae, | 0.25 to 1 |
| ATCC 29212 E. faecalis, | 8 to 32 | ATCC 29213 S. aureus, | 0.25 to 1 |
| ATCC 49247 H. influenzae, | 4 to 32 | ATCC 49619 S. pneumoniae, | 0.12 to 0.5 |
Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure requires the use of standardized inoculum concentrations. This procedure uses paper disks impregnated with 30-mcg tetracycline (as a class disk) or a 30-mcg demeclocycline hydrochloride disk to test the susceptibility of microorganisms to demeclocycline. Reports from the laboratory providing results of the standard single-disk susceptibility test with either a 30-mcg tetracycline-class disk or a 30-mcg demeclocycline disk should be interpreted according to the following criteria: For organisms other than species, and species:
Diffusion Techniques
2 Haemophilus Neisseria gonorrhoeae Streptococcus 2
| Zone Diameter (mm) | Interpretation |
| ≥ 19 | Susceptible (S) |
| 15 to 18 | Intermediate (I) |
| ≤ 14 | Resistant (R) |
For species: Haemophilus 2
| Zone Diameter (mm) | Interpretation |
| ≥ 29 | Susceptible (S) |
| 26 to 28 | Intermediate (I) |
| ≤ 25 | Resistant (R) |
For : N. gonorrhoeae 2
| Zone Diameter (mm) | Interpretation |
| ≥ 38 | Susceptible (S) |
| 31 to 37 | Intermediate (I) |
| ≤ 30 | Resistant (R) |
For species: Streptococcus 2
| Zone Diameter (mm) | Interpretation |
| ≥ 23 | Susceptible (S) |
| 19 to 22 | Intermediate (I) |
| ≤ 18 | Resistant (R) |
Interpretation should be as stated above for results using dilution techniques. Interpretation involves correlation of the diameter obtained in the disk test with the MIC for demeclocycline hydrochloride or tetracycline.
As with standardized dilution techniques, diffusion methods require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures. For the diffusion technique, the 30-mcg demeclocycline hydrochloride disk or the 30-mcg tetracycline-class disk should provide the following zone diameters in these laboratory test quality control strains: 2
| Microorganism | Zone Diameter (mm) |
| , ATCC 25922 E. coli | 18 to 25 |
| ATCC 49247 H. influenzae, | 14 to 22 |
| , ATCC 49226 N. gonorrhoeae | 30 to 42 |
| , ATCC 25923 S. aureus | 24 to 30 |
| , ATCC 49619 S. pneumoniae | 27 to 31 |
INDICATIONS & USAGE
To reduce the development of drug-resistant bacteria and maintain the effectiveness of demeclocycline hydrochloride tablets and other antibacterial drugs, demeclocycline hydrochloride 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. Demeclocycline hydrochloride is indicated in the treatment of infections caused by susceptible strains of the designated microorganisms in the conditions below:
Rocky Mountain spotted fever, typhus fever and the typhus group, Q fever, rickettsialpox, and tick fevers caused by rickettsiae; Respiratory tract infections caused by ; Lymphogranuloma venereum due to ; Psittacosis (Ornithosis) due to ; Trachoma due to , although the infectious agent is not always eliminated, as judged by immunofluorescence; Inclusion conjunctivitis caused by ; Nongonococcal urethritis in adults caused by or ; Relapsing fever due to ; Chancroid caused by ; Plague due to ; Tularemia due to ; Cholera caused by ; Campylobacter fetus infections caused by ; Brucellosis due to species (in conjunction with streptomycin); Bartonellosis due to ; Granuloma inguinale caused by ; Demeclocycline hydrochloride is indicated for treatment of infections caused by the following gram-negative microorganisms, when bacteriologic testing indicates appropriate susceptibility to the drug: ; ; species; species; Respiratory tract infections caused by ; Respiratory tract and urinary tract infections caused by species. Demeclocycline hydrochloride 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 pneumoniae; Skin and skin structure infections caused by . (Note: Tetracyclines, including demeclocycline, are not the drugs of choice in the treatment of any type of staphylococcal infection.) When penicillin is contraindicated, tetracyclines, including demeclocycline hydrochloride, are alternative drugs in the treatment of the following infections: Uncomplicated urethritis in men due to , and for the treatment of other uncomplicated gonococcal infections; Infections in women caused by ; Syphilis caused by subspecies ; Yaws caused by subspecies ; Listeriosis due to ; Anthrax due to ; Vincent’s infection caused by ; Actinomycosis caused by ; Clostridial diseases caused by species. In acute intestinal amebiasis, demeclocycline hydrochloride may be a useful adjunct to amebicides. In severe acne, demeclocycline hydrochloride may be a useful adjunctive therapy.
Mycoplasma pneumoniae
Chlamydia trachomatis
Chlamydia psittaci
Chlamydia trachomatis
Chlamydia trachomatis
Ureaplasma urealyticum Chlamydia trachomatis
Borrelia recurrentis
Haemophilus ducreyi
Yersinia pestis
Francisella tularensis
Vibrio cholerae
Campylobacter fetus
Brucella
Bartonella bacilliformis
Calymmatobacterium granulomatis
Escherichia coli
Enterobacter aerogenes
Shigella
Acinetobacter
Haemophilus influenzae
Klebsiella
Streptococcus
Staphylococcus aureus
Neisseria gonorrhoeae
Neisseria gonorrhoeae
Treponema pallidum pallidum
Treponema pallidum pertenue
Listeria monocytogenes
Bacillus anthracis
Fusobacterium fusiforme
Actinomyces israelii
Clostridium
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