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Vibramycin (Doxycycline Monohydrate) - Description and Clinical Pharmacology


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


Vibramycin is an antibacterial drug synthetically derived from oxytetracycline, and is available as Vibramycin Monohydrate (doxycycline monohydrate); Vibramycin Hyclate and Vibra-Tabs (doxycycline hydrochloride hemiethanolate hemihydrate); and Vibramycin Calcium (doxycycline calcium) for oral administration.

The structural formula of doxycycline monohydrate is

with a molecular formula of C22H24N2O8•H2O and a molecular weight of 462.46. The chemical designation for doxycycline 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 monohydrate. The molecular formula for doxycycline hydrochloride hemiethanolate hemihydrate is (C22H24N2O8•HCl)2•C2H6O•H2O and the molecular weight is 1025.89. Doxycycline is a light-yellow crystalline powder. Doxycycline hyclate is soluble in water, while doxycycline monohydrate is very slightly soluble in water.

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.

Inert ingredients in the syrup formulation are: apple flavor; butylparaben; calcium chloride; carmine; glycerin; hydrochloric acid; magnesium aluminum silicate; povidone; propylene glycol; propylparaben; raspberry flavor; simethicone emulsion; sodium hydroxide; sodium metabisulfite; sorbitol solution; water.

Inert ingredients in the capsule formulations are: hard gelatin capsules (which may contain Blue 1 and other inert ingredients); magnesium stearate; microcrystalline cellulose; sodium lauryl sulfate.

Inert ingredients for the oral suspension formulation are: carboxymethylcellulose sodium; Blue 1; methylparaben; microcrystalline cellulose; propylparaben; raspberry flavor; Red 28; simethicone emulsion; sucrose.

Inert ingredients for the tablet formulation are: ethylcellulose; hypromellose; magnesium stearate; microcrystalline cellulose; propylene glycol; sodium lauryl sulfate; talc; titanium dioxide; Yellow 6 Lake.


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 1–5%/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 18–22 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.


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 for VIBRAMYCIN.

Gram-Negative Bacteria

Acinetobacter species
Bartonella bacilliformis
Brucella species
Klebsiella species
Klebsiella granulomatis
Campylobacter fetus
Enterobacter aerogenes
Escherichia coli
Francisella tularensis
Haemophilus ducreyi
Haemophilus influenzae
Neisseria gonorrhoeae
Shigella species
Vibrio cholerae
Yersinia pestis

Gram-Positive Bacteria

Bacillus anthracis
Streptococcus pneumoniae

Anaerobic Bacteria

Clostridium species
Fusobacterium fusiforme
Propionibacterium acnes

Other Bacteria

Nocardiae and other aerobic Actinomyces species
Borrelia recurrentis
Chlamydophila psittaci
Chlamydia trachomatis
Mycoplasma pneumoniae
Treponema pallidum
Treponema pallidum subspecies pertenue
Ureaplasma urealyticum


Balantidium coli
Entamoeba species
Plasmodium falciparum 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.

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 test method1,2,4 (broth or agar). The MIC values should be interpreted according to criteria provided 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 method1,3,4. This procedure uses paper disks impregnated with 30-μg doxycycline to test the susceptibility of microorganisms to doxycycline. The disk diffusion interpretive criteria are provided in Table 1.

Anaerobic Techniques

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.

Table 1: Susceptibility Test Interpretive Criteria for Doxycycline and Tetracycline
Bacteria 1 Minimal Inhibitory Concentration
Zone Diameter
Agar Dilution
Acinetobacter spp.
  Doxycycline ≤4 8 ≥16 ≥13 10–12 ≤9 - - -
  Tetracycline ≤4 8 ≥16 ≥15 12–14 ≤11 - - -
  Tetracycline - - - - - - ≤4 8 ≥16
Bacillus anthracis 2
  Doxycycline ≤1 - - - - - - - -
  Tetracycline ≤1 - - - - - - - -
Brucella species
  Doxycycline ≤1 - - - - - - - -
  Tetracycline ≤1 - - - - - - - -
  Doxycycline ≤4 8 ≥16 ≥14 11–13 ≤10 - - -
  Tetracycline ≤4 8 ≥16 ≥15 12 –14 ≤11 - - -
Franciscella tularensis
  Doxycycline ≤ 4 - - - - - - - -
  Tetracycline ≤ 4 - - - - - - - -
Haemophilus influenzae
  Tetracycline ≤2 4 ≥8 ≥29 26–28 ≤25 - - -
Mycoplasma pneumoniae
  Tetracycline - - - - - - ≤2 - -
Nocardiae and other aerobic Actinomyces species
  Doxycycline ≤1 2–4 ≥8 - - - - - -
Neisseria gonorrhoeae 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 ≥ 16 mcg/mL)
  Tetracycline - - - ≥38 31–37 ≤30 ≤0.25 0.5–1 ≥2
Streptococcus pneumoniae
  Doxycycline ≤0.25 0.5 ≥1 ≥28 25–27 ≤24 - - -
  Tetracycline ≤1 2 ≥4 ≥28 25–27 ≤24
Vibrio cholerae
  Doxycycline ≤4 8 ≥16 - - - - - -
  Tetracycline ≤4 8 ≥16 - - - - - -
Yersinia pestis
  Doxycycline ≤4 8 ≥16 - - - - - -
  Tetracycline ≤4 8 ≥16 - - - - - -
Ureaplasma urealyticum
  Tetracycline - - - - - - ≤1 - ≥2

1 Organisms susceptible to tetracycline are also considered susceptible to doxycycline. However, some organisms that are intermediate or resistant to tetracycline may be susceptible to doxycycline
2 The current absence of resistance isolates precludes defining any results other than "Susceptible". If isolates yielding MIC results other than susceptible, they should be submitted to a reference laboratory for further testing.

A report of "Susceptible" (S) indicates that the antimicrobial drug is likely to inhibit growth of the microorgamism if the antimicrobial drug reaches the concentration usually achievable at the site of infection. 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 antimicrobial is not likely to inhibit growth of the pathogen if the antimicrobial drug reaches the concentrations usually achievable at the infection site; other therapy should be selected.

Quality Control

Standardized susceptibility test procedures require the use of laboratory controls to monitor and ensure the accuracy and precision of the 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 noted in Table 2 should be achieved.

Table 2: Acceptable Quality Control Ranges for Susceptibility Testing for Doxycycline and Tetracycline
QC Strain Minimal Inhibitory Concentration
Zone Diameter
Agar Dilution
Enterococcus faecalis ATCC 29212
  Doxycycline 2 – 8 - -
  Tetracycline 8 – 32 - -
Escherichia coli ATCC 25922
  Doxycycline 0.5 – 2 18 – 24 -
  Tetracycline 0.5 – 2 18 – 25 -
Eubacteria lentum ATCC 43055
  Doxycycline 2 – 16
Haemophilus influenzae ATCC 49247
  Tetracycline 4 – 32 14 – 22 -
Neisseria gonorrhoeae ATCC 49226
  Tetracycline - 30 – 42 0.25 – 1
Staphylococcus aureus ATCC 25923
  Doxycycline - 23 – 29 -
  Tetracycline - 24 – 30 -
Staphylococcus aureus ATCC 29213
  Doxycycline 0.12 –0.5 - -
  Tetracycline 0.12 – 1 - -
Streptococcus pneumoniae ATCC 49619
  Doxycycline 0.015 – 0.12 25 – 34 -
  Tetracycline 0.06 – 0.5 27 – 31 -
Bacteroides fragilis ATCC 25285
  Tetracycline - - 0.12 – 0.5
Bacteroides thetaiotaomicron ATCC 29741
  Doxycycline 2 – 16
  Tetracycline - - 8 – 32
Mycoplasma pneumoniae ATCC 29342
  Tetracycline 0.06–0.5 - 0.06–0.5
Ureaplasma urealyticum ATCC 33175
  Tetracycline - - ≥8


Hyperpigmentation of the thyroid has been produced by members of the tetracycline class in the following species: in rats by oxytetracycline, doxycycline, tetracycline PO4, and methacycline; in minipigs by doxycycline, minocycline, tetracycline PO4, and methacycline; in dogs by doxycycline and minocycline; in monkeys by minocycline.

Minocycline, tetracycline PO4, methacycline, doxycycline, tetracycline base, oxytetracycline HCl, and tetracycline HCl were goitrogenic in rats fed a low iodine diet. This goitrogenic effect was accompanied by high radioactive iodine uptake. Administration of minocycline also produced a large goiter with high radioiodine uptake in rats fed a relatively high iodine diet.

Treatment of various animal species with this class of drugs has also resulted in the induction of thyroid hyperplasia in the following: in rats and dogs (minocycline); in chickens (chlortetracycline); and in rats and mice (oxytetracycline). Adrenal gland hyperplasia has been observed in goats and rats treated with oxytetracycline.

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