Demeclocycline Hydrochloride

DEMECLOCYCLINE HYDROCHLORIDE- demeclocycline hydrochloride tablet
Amneal Pharmaceuticals LLC

DESCRIPTION

Demeclocycline HCl 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:

Demeclocycline HCl tablets, USP, for oral administration, contain 150 mg or 300 mg of demeclocycline HCl, USP 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

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 HCl 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 HCl penetrates well into various body fluids and tissues. The percent of demeclocycline HCl bound to plasma protein is about 40% using a dialysis equilibrium method and 90% using an ultra-filtration method. Demeclocycline HCl, 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 HCl renal clearance (35 mL/min/1.73 m²) is less than half that of tetracycline. Following a single 150 mg dose of demeclocycline HCl 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

Calymmatobacterium granulomatis

Campylobacter fetus

Francisella tularensis

Haemophilus ducreyi

Haemophilus influenzae

Neisseria gonorrhoeae

Vibrio cholerae

Yersinia pestis

Because 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

Borrelia recurrentis

Chlamydia psittaci

Chlamydia trachomatis

Clostridium species

Entamoeba species

Fusobacterium fusiforme

Mycoplasma pneumoniae

Propionibacterium acnes

Rickettsiae

Treponema pallidum subspecies pallidum

Treponema pallidum subspecies pertenue

Ureaplasma urealyticum

Susceptibility Test Methods

For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.fda.gov/STIC.

INDICATIONS AND USAGE

Demeclocycline HCl tablets are 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 Mycoplasma pneumoniae

Lymphogranuloma venereum due to Chlamydia trachomatis

Psittacosis (Ornithosis) due to Chlamydia psittaci

Trachoma due to Chlamydia trachomatis , although the infectious agent is not always eliminated as judged by immunofluorescence

Inclusion conjunctivitis caused by Chlamydia trachomatis

Nongonococcal urethritis in adults caused by Ureaplasma urealyticum or Chlamydia trachomatis

Relapsing fever due to Borrelia recurrentis

Chancroid caused by Haemophilus ducreyi

Plague due to Yersinia pestis

Tularemia due to Francisella tularensis

Cholera caused by Vibrio cholerae

Campylobacter fetus infections cause by Campylobacter fetus

Brucellosis due to Brucella species (in conjunction with streptomycin);

Bartonellosis due to Bartonella bacilliformis

Granuloma inguinale caused by Calymmatobacterium granulomatis

Demeclocycline HCl tablets are indicated for treatment of infections by the following gram-negative microorganisms, when bacteriologic testing indicates appropriate susceptibility to the drug:

Escherichia coli

Enterobacter aerogenes

Shigella species

Acinetobacter species

Respiratory tract infections caused by Haemophilus influenzae

Respiratory tract and urinary tract infections caused by Klebsiella species

Demeclocycline HCl tablets are 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

Skin and skin structure infections caused by Staphylococcus aureus. (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 HCl, are alternative drugs in the treatment of the following infections:

Uncomplicated urethritis in men due to Neisseria gonorrhoeae , and for the treatment of other uncomplicated gonococcal infections

Infections in women caused by Neisseria gonorrhoeae

Syphilis caused by Treponema pallidum subspecies pallidum

Yaws caused by Treponema pallidum subspecies pertenue

Listeriosis due to Listeria monocytogenes

Anthrax due to Bacillus anthracis

Vincent’s infection caused by Fusobacterium fusiforme

Actinomycosis caused by Actinomyces israelii

Clostridial diseases caused by Clostridium species

In acute intestinal amebiasis, demeclocycline HCl may be a useful adjunct to amebicides.

In severe acne, demeclocycline HCl may be a useful adjunctive therapy.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of demeclocycline HCl tablets and other antibacterial drugs, demeclocycline HCl 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.