Doxycycline Hyclate

DOXYCYCLINE HYCLATE- doxycycline hyclate capsule
TYA Pharmaceuticals

D oxycycline Hyclate Capsules USP

Doxycycline Hyclate Tablets USP

Revised: June 2012

Rx only

To reduce the development of drug-resistant bacteria and maintain the effectiveness of doxycycline hyclate and other antibacterial drugs, doxycycline hyclate should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

DESCRIPTION

Doxycycline is a broad-spectrum antibiotic synthetically derived from oxytetracycline, and is available as doxycycline hyclate (doxycycline hydrochloride hemiethanolate hemihydrate) for oral administration.

The structural formula of doxycycline hyclate is

structural formula of doxycycline hyclate
(click image for full-size original)

with a molecular formula of (C H N O •HCl) •C H O•H O and a molecular weight of 1025.89. The chemical designation for doxycycline hyclate is 4-(Dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-2-naphthacenecarboxamide monohydrochloride, compound with ethyl alcohol (2:1), monohydrate. Doxycycline hyclate is a yellow crystalline powder which is soluble in water. 22 24 2 8 2 2 6 2

Doxycycline has a high degree of lipoid solubility and a low affinity for calcium binding. It is highly stable in normal human serum. Doxycycline will not degrade into an epianhydro form.

Each capsule, for oral administration, contains Doxycycline Hyclate, equivalent to 50 mg or 100 mg of Doxycycline.

Each tablet, for oral administration, contains Doxycycline Hyclate, equivalent to 100 mg of Doxycycline.

Doxycycline Hyclate Capsules USP 50 mg and 100 mg contain the following inactive ingredients: magnesium stearate and microcrystalline cellulose.

The capsule shells contain: FD&C Blue No. 1, gelatin, silicon dioxide, sodium lauryl sulfate and titanium dioxide.

Doxycycline Hyclate Tablets USP 100 mg contain the following inactive ingredients: croscarmellose sodium, FD&C Red No. 40, FD&C Yellow No. 6, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polysorbate 80, sodium lauryl sulfate and titanium dioxide.

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 to 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.

Results of animal studies indicate that tetracyclines cross the placenta and are found in fetal tissues.

Microbiology

The tetracyclines are primarily bacteriostatic and are thought to exert their antimicrobial effect by the inhibition of protein synthesis. The tetracyclines, including doxycycline, have a similar antimicrobial spectrum of activity against a wide range of gram-positive and gram-negative organisms. Cross-resistance of these organisms to tetracyclines is common.

Gram-Negative Bacteria

  • Neisseria gonorrhoeae
  • Calymmatobacterium granulomatis
  • Haemophilus ducreyi
  • Haemophilus influenzae
  • formerly Yersinia pestis ( Pasteurella pestis)
  • formerly Francisella tularensis ( Pasteurella tularensis)
  • formerly Vibrio cholera e ( Vibrio comma)
  • Bartonella bacilliformis
  • species Brucella

Because many strains of the following groups of gram-negative microorganisms have been shown to be resistant to tetracyclines, culture and susceptibility testing are recommended:

  • Escherichia coli
  • species Klebsiella
  • Enterobacter aerogenes
  • species Shigella
  • species formerly species species Acinetobacter ( Mima and Herellea )
  • species Bacteroides

Gram-Positive Bacteria

Because many strains of the following groups of gram-positive microorganisms have been shown to be resistant to tetracycline, culture and susceptibility testing are recommended. Up to 44 percent of strains of and 74 percent of have been found to be resistant to tetracycline drugs. Therefore, tetracycline should not be used for streptococcal disease unless the organism has been demonstrated to be susceptible. Streptococcus pyogenes Streptococcus faecalis

  • Streptococcus pyogenes
  • Streptococcus pneumoniae
  • Enterococcus group (Streptococcus faecalis and Streptococcus faecium)
  • Alpha-hemolytic streptococci (viridans group)

Other Microorganisms

  • Rickettsiae

  • Chlamydia psittaci

  • Chlamydia trachomatis

  • Mycoplasma pneumoniae

  • Ureaplasma urealyticum

  • Borrelia recurrentis

  • Treponema pallidum

  • Treponema pertenue

  • species Clostridium

  • Fusobacterium fusiforme

  • species Actinomyces

  • Bacillus anthracis

  • Propionibacterium acnes

  • species Entamoeba

  • Balantidium coli

  • Plasmodium falciparum

Doxycycline has been found to be active against the asexual erythrocytic forms of , but not against the gametocytes of . The precise mechanism of action of the drug is not known. Plasmodium falciparum P. falciparum

Suscep tibility tests:

Diffusion techniques:

Quantitative methods that require measurement of zone diameters give the most precise estimate of the susceptibility of bacteria to antimicrobial agents. One such standard procedure which has been recommended for use with disks to test susceptibility of organisms to doxycycline uses the 30-mcg tetracycline-class disk or the 30-mcg doxycycline disk. Interpretation involves the correlation of the diameter obtained in the disk test with the minimum inhibitory concentration (MIC) for tetracycline or doxycycline, respectively. 1

Reports from the laboratory giving results of the standard single-disk susceptibility test with a 30-mcg tetracycline-class disk or the 30-mcg doxycycline disk should be interpreted according to the following criteria:

Zone diameter (mm) Interpretation
tetracycline doxycycline
≥ 19 ≥ 16 Susceptible
15 to 18 13 to 15 Intermediate
≤ 14 ≤ 12 Resistant

A report of “Susceptible” indicates that the pathogen is likely to be inhibited by generally achievable blood levels. A report of “Intermediate” suggests that the organism would be susceptible if a high dosage is used or if the infection is confined to tissues and fluids in which high antimicrobial levels are attained. A report of “Resistant” indicates that achievable concentrations are unlikely to be inhibitory, and other therapy should be selected.

Standardized procedures require the use of laboratory control organisms. The 30-mcg tetracycline-class disk or the 30-mcg doxycycline disk should give the following zone diameters:

Organism Zone Diameter (mm)
tetracycline doxycycline
ATCC 25922 E. coli 18 to 25 18 to 24
ATCC 25923 S. aureus 19 to 28 23 to 29

Dilution techniques:

Use a standardized dilution method (broth, agar, microdilution) or equivalent with tetracycline powder. The MIC values obtained should be interpreted according to the following criteria: 2

MIC (mcg/mL) Interpretation
≤ 4 Susceptible
8 Intermediate
≥ 16 Resistant

As with standard diffusion techniques, dilution methods require the use of laboratory control organisms. Standard tetracycline powder should provide the following MIC values:

Organism MIC (mcg/mL)
ATCC 25922 E. coli 1 to 4
ATCC 29213 S. aureus 0.25 to 1
ATCC 29212 E. faecalis 8 to 32
ATCC 27853 P. aeruginosa 8 to 32

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