Doxycycline: Package Insert and Label Information

DOXYCYCLINE — doxycycline capsule
Alembic Pharmaceuticals Limited


Doxycycline, USP is a broad — spectrum antibacterial synthetically derived from oxytetracycline. Doxycycline monohydrate capsules USP, 100 mg and 75 mg contain doxycycline monohydrate equivalent to 100 mg and 75 mg of doxycycline for oral administration. The chemical designation of the light yellow to pale yellow powder is alpha- 6- deoxy- 5- oxytetracycline.

Structural formula:

(click image for full-size original)

C22 H24 N2 O8 • H2 O M.W. = 462.45

Doxycycline has a high degree of lipid 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: microcrystalline cellulose; sodium starch glycolate; povidone; colloidal silicon dioxide; magnesium stearate; and a hard gelatin capsule which contains iron oxide black, iron oxide red, iron oxide yellow, titanium dioxide, gelatin and sodium lauryl sulphate. The capsule shells of 75 mg are printed with edible black ink containing shellac, propylene glycol, iron oxide black and potassium hydroxide. The cap of 100 mg capsule shells is printed with edible white ink containing shellac, propylene glycol, potassium hydroxide and titanium dioxide. The body of 100 mg capsule shells is printed with edible and brown ink containing shellac, propylene glycol, potassium hydroxide, iron oxide brown and iron oxide black.


Tetracyclines are readily absorbed and are bound to plasma proteins in varying degrees. They are concentrated by the liver in the bile and excreted in the urine and feces at high concentrations in a biologically active form. Doxycycline is virtually completely absorbed after oral administration.

Following a 200 mg dose of doxycycline monohydrate, 24 normal adult volunteers averaged the following serum concentration values:

Time (hr): 0.5 1 1.5 2 3 4 8 12 24 48 72
Conc. 1.02 2.26 2.67 3.01 3.16 3.03 2.03 1.62 0.95 0.37 0.15 (μg/mL)

Average Observed Values

Maximum Concentration 3.61 μg/mL (± 0.9 sd)

Time of Maximum Concentration 2.6 hr (± 1.1 sd)

Elimination Rate Constant 0.049 per hr (± 0.03 sd)

Half-Life 16.33 hr (± 4.53 sd)

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.
Mechanism of Action

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.
Antimocrobial Activity

Doxycycline has been shown to be active against most isolates of the following microorganisms, both in vitro and in clinical infections (see INDICATIONS AND USAGE).

Gram-Negative Bacteria

Acinetobacter species

Bartonella bacilliformis

Brucella species

Campylobacter fetus

Enterobacter aerogenes

Escherichia coli

Francisella tularensis

Haemophilus ducreyi

Haemophilus influenza

Klebsiella granulomatis

Klebsiella species

Neisseria gonorrhoeae

Shigella species

Vibrio cholerae

Yersinia pestis

Gram-Positive Bacteria

Bacillus anthracis

Listeria monocytogenes

Streptococcus pneumoniae

Anaerobic Bacteria

Clostridium species

Fusobacterium fusiforme

Propionibacterium acnes
Other Bacteria

Nocardiae and other Actinomyces species

Borrelia recurrentis

Chlamydophila psittaci

Chlamydia trachomatis

Mycoplasma pneumoniae


Treponema pallidum

Treponema pallidum subspecies pertenue

Ureaplasma urealyticum


Balantidium coli

Entamoeba species
Susceptibility Testing Methods

When available, the clinical microbiology laboratory should provide cumulative reports of in vitro susceptibility test results for antimicrobial drugs used in local hospitals and practice areas 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 method (broth and/or agar).1,2,4,6,7 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 should be determined using a standardized test method.1,3,4 This procedure uses paper disks impregnated with 30 mcg 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 method.1,5 The MIC values obtained should be interpreted according to the criteria provided in Table 1Table 1: Susceptibility Test Interpretive Criteria for Doxycycline and Tetracycline

Bacteria* Minimal Inhibitory Concentration (mcg per mL) Zone Diameter (mm) Agar Dilution (mcg per mL)
Acinetobacter spp. Doxycycline Tetracycline ≤4≤4 8 8 ≥16≥16 ≥13≥15 10 to 12 12 to 14 ≤9≤11 — – — – — –
Anaerobes Tetracycline ≤4 8 ≥16
Bacillus anthracis Doxycycline Tetracycline ≤1≤1 — – — – — – — – — – — – — – — –
Brucella species Doxycycline Tetracycline ≤1≤1 — – — – — – — – — – — – — – — –
Enterobacteriaceae Doxycycline Tetracycline ≤4≤4 8 8 ≥16≥16 ≥14≥15 11 to 13 12 to 14 ≤10≤11 — – — – — –
Franciscella tularensis Doxycycline Tetracycline ≤4≤4 — – — – — – — – — – — – — – — –
Haemophilus influenzae Tetracycline ≤2 4 ≥8 – ≥29 -26 to 28 – ≤25
Mycoplasma pneumoniae Tetracycline ≤2
Neisseria gonorrhoeae Tetracycline ≥38 31 to 37 ≤30 ≤0.25 0.5 to 1 ≥2
Norcardiae and other aerobic Actinomyces species Doxycycline ≤1 2 to 4 ≥8
Streptococcus pneumonia Doxycycline Tetracycline <0.25≤1 0.52 ≥1 ≥4 ≥28 ≥28 25 to 2725 to 27 <24≤24
Vibrio cholerae Doxycycline Tetracycline ≤4≤4 8 8 ≥16≥16 — – — – — – — – — – — –
Yersinia pestis Doxycycline Tetracycline ≤4≤4 8 8 ≥16≥16 — – — – — – — – — – — –
Ureaplasma urealyticum Tetracycline ≤1 ≥2

* 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.

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.

Gonococci with 30 mcg tetracycline disk zone diameters of less than 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 per mL).

A report of Susceptible (S) indicates that the antimicrobial is likely to inhibit growth of the microorganism if the antimicrobial drug reaches the concentrations usually achievable at the site of infection. A report of Intermediate (I) 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 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 drug is not likely to inhibit growth of the microorganism 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 test.1,2,3,4,5,6,7 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 or 30 mcg tetracycline disk, the criteria noted in should be achieved.

Table 2: Acceptable Quality Control Ranges for Susceptibility Testing for Doxycycline and Tetracycline

QC Strain Minimal Inhibitory Concentration (mcg per mL) Zone Diameter (mm) Agar Dilution (mcg per mL)
Enterococcus faecalis ATCC 29212 Doxycycline Tetracycline 2 to 8 8 to 32 — – — –
Escherichia coli ATCC 25922 Doxycycline Tetracycline 0.5 to 2 0.5 to 2 18 to 24 18 to 25 — –
Eggerthella lenta ATCC43055Doxycycline 2 to 16
Haemophilus influenzae ATCC 49247 Tetracycline 4 to 32 14 to 22
Neisseria gonorrhoeae ATCC 49226 Tetracycline 30 to 42 0.25 to 1
Staphylococcus aureus ATCC 25923 Doxycycline Tetracycline — – 23 to 29 24 to 30 — –
Staphylococcus aureus ATCC 29213 Doxycycline Tetracycline 0.12 to 0.5 0.12 to 1 — – — –
Streptococcus pneumoniae ATCC 49619 Doxycycline Tetracycline 0.015 to 0.12 0.06 to 0.5 25 to 34 27 to 31 — –
Bacteroides fragilis ATCC 25285 Tetracycline 0.125 to 0.5
Bacteroides thetaiotaomicron ATCC 29741 DoxycyclineTetracycline 2 to 8- 8 to 32
Mycoplasma pneumoniae ATCC 29342 Tetracycline 0.06 to 0.5 0.06 to 0.5
Ureaplasma urealyticum ATCC 33175 Tetracycline ≥8

* ATCC is the American Type Culture Collection

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