Tetracycline Hydrochloride

TETRACYCLINE HYDROCHLORIDE- tetracycline hydrochloride capsule
TETRACYCLINE HYDROCHLORIDE — tetracycline hydrochloride capsule
AvKARE

DESCRIPTION

Tetracycline is a yellow, odorless, crystalline powder. Tetracycline is stable in air but exposure to strong sunlight causes it to darken. Its potency is affected in solutions of pH below 2 and is rapidly destroyed by alkali hydroxide solutions. Tetracycline is very slightly soluble in water, freely soluble in dilute acid and in alkali hydroxide solutions, sparingly soluble in alcohol, and practically insoluble in chloroform and in ether. The chemical name for tetracycline hydrochloride is 4-(Dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,6,10,12,-12a-pentahydroxy-6-methyl-1,11-dioxo-2-naphthacenecar-boxamide monohydrochloride. Its structural formula is as follows:

S:\REGULATORY AFFAIRS\ANDA_NDA\Tetracycline\0006\docs\fig 1.jpg
(click image for full-size original)

Each capsule, for oral administration, contains 250 mg or 500 mg tetracycline hydrochloride.

Inactive Ingredients: Lactose, light mineral oil, and magnesium stearate.

The 250 mg and 500 mg capsule shells contain D&C yellow no. 10, FD&C blue no. 1, FD&C yellow no. 6, gelatin, and titanium dioxide.

The imprinting ink for the 250 mg and 500 mg capsules contains D&C yellow #10, FD&C blue no. 1, FD&C blue no. 2, FD&C red no. 40, iron oxide black, pharmaceutical shellac glaze, propylene glycol and n-butyl alcohol.

CLINICAL PHARMACOLOGY

Tetracyclines are readily absorbed and are bound to plasma protein 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.

Microbiology

Tetracyclines are primarily bacteriostatic and exert their antimicrobial effect by the inhibition of protein synthesis by binding to the 30S ribosomal subunit. Tetracycline is active against a broad range of gram-negative and gram-positive organisms. The drugs in the tetracycline class have closely similar antimicrobial spectra, and cross-resistance among them is common.

Tetracycline has been shown to be active against most isolates of the following bacteria, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section of the package insert.

Gram-negative Bacteria

Acinetobacter species

Bartonella bacilliformis

Brucella species

Campylobacter fetus

Enterobacter aerogenes

Escherichia coli

Francisella tularensis

Haemophilus ducreyi

Haemophilus influenzae

Klebsiella species

Klebsiella granulomatis

Neisseria gonorrhoeae

Shigella species

Vibrio cholerae

Yersinia pestis

Gram-positive Bacteria

Bacillus anthracis

Streptococcus pyogenes

Streptococcus pneumoniae

Staphylococcus aureus

Listeria monocytogenes

Anaerobes

Bacteroides species

Clostridium species

Fusobacterium fusiforme

Propionibacterium acnes

Other Bacteria

Actinomyces species

Borrelia recurrentis

Chlamydophila psittaci

Chlamydia trachomatis

Rickettsiae

Treponema pallidum

Treponema pallidum subspecies pertenue

Parasites

Entamoeba species

Balantidium coli

Susceptibility Test 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 method 1,2,4 (broth and/or agar). The MIC values should be interpreted according to the 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 standard test method 1,3,4. This procedure uses paper disks impregnated with 30 mcg tetracycline to test the susceptibility of bacteria to tetracycline. The disk diffusion interpretive criteria are provided in Table 1.

Anaerobic Techniques

For anaerobic bacteria, the susceptibility to tetracycline can be determined by a standardized test method 5. The MIC values obtained should be interpreted according to the criteria provided in Table 1.

Table 1: Susceptibility Test Interpretive Criteria for Tetracycline
Bacteria a Minimal Inhibitory Concentration (mcg/mL) Zone Diameter (mm) Agar Dilution (mcg/mL)
S I R S I R S I R
a 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.
b 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 greater than or equal to 16 mcg/mL).
Acinetobacter spp. <4 8 >16 >15 12-14 <11
Anaerobes <4 8 >16
Bacillus anthracis a <1
Brucella species a <1
Enterobacteriaceae <4 8 >16 >15 12-14 <11
Franciscella tularensis a <4
Haemophilus influenzae <2 4 >8 >29 26-28 <25
Mycoplasma pneumoniae ≤2
Neisseria gonorrhoeae b >38 31-37 <30 <0.25 0.5-1 >2
Staphylococcus aureus <4 8 >16 >19 15-18 <14
Streptococcus pneumoniae <1 2 >4 >28 25-27 <24
Streptococcus pyogenes <2 4 >8 >23 19-22 <18
Vibrio cholerae <4 8 >16
Yersinia pestis <4 8 >16

A report of Susceptible (S) indicates that the antimicrobial is likely to inhibit growth of the pathogen if the antimicrobial compound 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 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 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 compound 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 tetracycline powders should provide the following range of MIC values noted in Table 2. For the diffusion technique using the 30 mcg tetracycline disk the criteria noted in Table 2 should be achieved.

Table 2: Acceptable Quality Control Ranges for Susceptibility Testing for Tetracycline
QC Strain Minimal Inhibitory Concentration (mcg/mL) Zone Diameter (mm) Agar Dilution (mcg/mL)
Enterococcus faecalis ATCC 29212 8 — 32
Escherichia coli ATCC 25922 0.5 — 2 18 — 25
Haemophilus influenzae ATCC 49247 4 — 32 14 — 22
Mycoplasma pneumonia ATCC 29342 0.06 — 0.5 0.06 — 0.5
Neisseria gonorrhoeae ATCC 49226 30 — 42 0.25 — 1
Staphylococcus aureus ATCC 25923 24 — 30
Staphylococcus aureus ATCC 29213 0.12 — 1
Streptococcus pneumoniae ATCC 49619 0.06 — 0.5 27 — 31
Bacteroides fragilis ATCC 25285 0.12 — 0.5
Bacteroides thetaiotaomicron ATCC 29741 8 — 32
Page 1 of 4 1 2 3 4

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2022. All Rights Reserved.