Demeclocycline Hydrochloride
DEMECLOCYCLINE HYDROCHLORIDE- demeclocycline hydrochloride tablet, film coated
Marlex Pharmaceuticals Inc
DEMECLOCYCLINE HYDROCHLORIDE- demeclocycline hydrochloride tablet, film coated
Marlex Pharmaceuticals, Inc.
Demeclocycline Hydrochloride Tablets Rx Only
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, USP is an antibiotic isolated from a mutant strain of Streptomyces aureofaciens. 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:
Each film-coated tablet, for oral administration contains 150 mg or 300 mg of demeclocycline hydrochloride, USP and has the following inactive ingredients: carnauba wax, colloidal silicon dioxide, crospovidone, hydroxypropyl cellulose, hypromelloses, magnesium stearate, microcrystalline cellulose, polydextrose, polyethylene glycol, pregelatinized starch, talc, titanium dioxide, triacetin, D&C Red No. 27 Aluminum Lake, D&C Red No. 30 Aluminum Lake, FD&C Blue No. 1 Aluminum Lake and FD&C Yellow No. 6 Aluminum Lake.
CLINICAL PHARMACOLOGY
Pharmacokinetics
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. 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 m2) 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.
Microbiology
Mechanism of Action
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.
Mechanism(s) of Resistance
Resistance to tetracyclines may be mediated by efflux, alteration in the target site of tetracycline, enzymatic inactivation, and decreased bacterial permeability to the tetracycline or a combination of these mechanisms.
Cross-Resistance
Cross-resistance between antibiotics of the tetracycline family occurs.
Demeclocycline has been shown to be active against most isolates of the following bacteria, in vitro and/or in clinical infections as described in the INDICATIONS AND USAGE section.
Gram-Positive Bacteria
Bacillus anthracis
Listeria monocytogenes Staphylococcus aureus
Streptococcus pneumoniae
Gram-Negative Bacteria
Bartonella bacilliformis
Brucella species
Calymmatobacterum granulomatis
Campylobacter fetus
Francisella tularensis Haemophilus ducreyi Haemophilus influezae Neisseria gonorrrhoeae Vibrio cholerae Yersinia pestis
Because many isolates of the following groups of gram-negative bacteria have been shown to be resistant to tetracyclines, culture and susceptibility testing are especially recommended:
Acinetobacter species
Enterobacter aerogenes
Escherichia coli Klebsiella species Shigella species
Other Microorganisms
Actinomyces israelii
Borella recurrentis
Chlamydia psittaci Chlamydia trachomatis Clostridium species Entamoeba species Fusobacterium fusiforme Mycoplasma pneumoniae Propionibacterium acnes Rickettsiae Treponema pallidium subspecies pallidum Treponema pallidum subspecies pertenue Ureaplasma urealyticum
Susceptibility Test Methods
When available, the clinical microbiology laboratory should provide the results of in vitro susceptibility test results for antimicrobial drug products 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 an antibacterial drug product for treatment
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 method (broth/or agar)1,2,3. The MIC values should be interpreted according to the criteria in Table 1.
Diffusion Techniques
Quantitative methods that require measurement of zone diameters can also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. The zone size provides an estimate of the susceptibility of bacteria to antimicrobial compounds.
The zone size should be determined using a standardized test method.2,4 This procedure uses paper disks impregnated with 30 mcg tetracycline to test the susceptibility of microorganisms to tetracycline. The disc diffusion interpretive criteria are provided in Table 1.
| Minimum Inhibitory Concentration (mcg/mL) | Disk Diffusion(zone diameters in mm) | |||||
| Pathogen | S | I | R | S | I | R |
| Enerobacteriacea, Acinetobacter spp. | ≤4 | 8 | >16 | ≥15 | 12 to 14 | <11 |
| Haemophilus influenzae | <2 | 4 | >8 | >29 | 26 to 28 | <25 |
| Neisseria gonorrhoeae | <0.25 | 0.5 to 1 | >2 | >38 | 31 to 37 | <30 |
| Staphylococcus aureus | ≤4 | 8 | ≥16 | ≥19 | 15 to 18 | ≤14 |
| S. pneumoniae (non-meningitis isolates) | ≤1 | 2 | ≥4 | >28 | 25 to 27 | ≤24 |
| Bacillus anthracis | <1 | — | — | — | — | — |
| Franciscella tularensis | <4 | — | — | — | — | — |
A report of Susceptible indicates that the antimicrobial is likely to inhibit growth of the pathogen if the antimicrobial compound reaches the concentrations at the infection site necessary to inhibit growth of the pathogen. A report of Intermediate 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 product is physiologically concentrated or in situations where a high dosage of the drug product 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 indicates that the antimicrobial 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.
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