Doxycycline Oral Suspension

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.

Microbiology

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 Doxycycline for Oral Suspension, USP.

Gram-Negative Bacteria

Acinetobacter species
Bartonella bacilliformis
Brucella species
Calymmatobacterium granulomatis
Campylobacter fetus
Enterobacter aerogenes
Escherichia coli
Francisella tularensis
Haemophilus ducreyi
Haemophilus influenzae
Klebsiella species
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
Rickettsiae
Treponema pallidum
Treponema pertenue
Ureaplasma urealyticum

Parasites

Balantidium coli
Entamoeba species
Plasmodium falciparum1

1 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 method 1,2,4 (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 method 1,3,4. 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*	Minimal Inhibitory Concentration (mcg/mL)			Zone Diameter (mm)			Agar Dilution (mcg/mL)
	S	I	R	S	I	R	S	I	R
* 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 < 19mm 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)
Acinetobacter spp.
Doxycycline	≤ 4	8	≥ 16	≥ 13	10-12	≤ 9	-	-	-
Tetracycline	≤ 4	8	≥ 16	≥ 15	12-14	≤ 11	-	-	-
Anaerobes
Tetracycline	-	-	-	-	-	-	≤ 4	8	≥ 16
Bacillus anthracis*†
Doxycycline	≤ 1	-	-	-	-	-	-	-	-
Tetracycline	≤ 1	-	-	-	-	-	-	-	-
Brucella species*†
Doxycycline	≤ 1	-	-	-	-	-	-	-	-
Tetracycline	≤ 1	-	-	-	-	-	-	-	-
Enterobacteriaceae
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‡
Tetracycline	-	-	-	≥ 38	31-37	≤ 30	≤ 0.25	0.5-1	≥ 2
Streptococcus pneumoniae
Tetracycline	≤ 2	4	≥ 8	≥ 23	19-22	≤ 18	-	-	-
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

A report of Susceptible (S) indicates that the antimicrobial is likely to inhibit growth of the pathogen if the antimicrobial compound reaches the concentrations at the infection site necessary to inhibit growth of the pathogen. 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 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 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 mcg/mL	Zone Diameter (mm)	Agar Dilution (mcg/mL)
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	-
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
Tetracycline	-	-	8 - 32
Mycoplasma pneumoniae ATCC 29342
Tetracycline	0.06 - 0.5	-	0.06 - 0.5
Ureaplasma urealyticum ATCC 33175
Tetracycline	-	-	≥ 8

To reduce the development of drug-resistant bacteria and maintain effectiveness of Doxycycline for Oral Suspension, USP and other antibacterial drugs, Doxycycline for Oral Suspension, USP 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.

Treatment

Doxycycline is indicated for the treatment of the following infections:

• 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 caused by Chlamydia trachomatis.
• Psittacosis (ornithosis) caused by Chlamydophila psittaci.
• Trachoma caused by Chlamydia trachomatis, although the infectious agent is not always eliminated, as judged by immunofluorescence.
• Inclusion conjunctivitis caused by Chlamydia trachomatis.
• Uncomplicated urethral, endocervical, or rectal infections in adults caused by Chlamydia trachomatis.
• Nongonococcal urethritis caused by Ureaplasma urealyticum.
• Relapsing fever due to Borrelia recurrentis.

Doxycycline is also indicated for the treatment of infections caused by the following gram-negative microorganisms:

• Chancroid caused by Haemophilus ducreyi.
• Plague due to Yersinia pestis.
• Tularemia due to Francisella tularensis.
• Cholera caused by Vibrio cholerae.
• Campylobacter fetus infections caused by Campylobacter fetus (formerly Vibrio fetus).
• Brucellosis due to Brucella species (in conjunction with streptomycin).
• Bartonellosis due to Bartonella bacilliformis.
• Granuloma inguinale caused by Calymmatobacterium granulomatis.

Because many strains of the following groups of microorganisms have been shown to be resistant to doxycycline, culture and susceptibility testing are recommended.

Doxycycline is indicated for treatment of infections caused by the following gram-negative bacteria, when bacteriologic testing indicates appropriate susceptibility to the drug:

• Escherichia coli.
• Enterobacter aerogenes (formerly Aerobacter aerogenes).
• Shigella species.
• Acinetobacter species.
• Respiratory tract infections caused by Haemophilus influenzae.
• Respiratory tract and urinary tract infections caused by Klebsiella species.

Doxycycline is 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 (formerly Diplococcus pneumoniae).
• Anthrax due to Bacillus anthracis, including inhalational anthrax (post-exposure): to reduce the incidence or progression of disease following exposure to aerosolized Bacillus anthracis.

When penicillin is contraindicated, doxycycline is an alternative drug in the treatment of the following infections:

• Uncomplicated gonorrhea caused by Neisseria gonorrhoeae.
• Syphilis caused by Treponema pallidum.
• Yaws caused by Treponema pertenue.
• Listeriosis due to Listeria monocytogenes.
• Vincent's infection caused by Fusobacterium fusiforme.
• Actinomycosis caused by Actinomyces israelii.
• Infections caused by Clostridium species.

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

In severe acne, doxycycline may be useful adjunctive therapy.

Prophylaxis

Doxycycline is indicated for the prophylaxis of malaria due to Plasmodium falciparum in short-term travelers (<4 months) to areas with chloroquine and/or pyrimethamine-sulfadoxine resistant strains. (See DOSAGE AND ADMINISTRATION section and Information for Patients subsection of the PRECAUTIONS section.)

This drug is contraindicated in persons who have shown hypersensitivity to any of the tetracyclines.

1. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing; Twenty-third Informational Supplement, CLSI document M100-S23. CLSI document M100-S23, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2013. 2. Clinical and Laboratory Standards Institute (CLSI). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard - Ninth Edition. CLSI document M07-A9, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2012 3. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Disk Diffusion Susceptibility Tests; Approved Standard -Eleventh Edition. CLSI document M02-A 11, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2012. 4. Clinical and Laboratory Standards Institute (CLSI). Methods for Antimicrobial Dilution and Disk Susceptibility Testing of Infrequently Isolated or Fastidious Bacteria; Approved Guideline -Second Edition. CLSI document M45-A2, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2010. 5. Clinical and Laboratory Standards Institute (CLSI). Methods for Antimicrobial Susceptibility Testing of Anaerobic Bacteria; Approved Standard – Eighth Edition. CLSI document M11-A8. Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, PA 19087 USA, 2012. 6. Clinical and Laboratory Standards Institute. Susceptibility Testing of Mycobacteria, Nocardiae, and Other Aerobic Actinomycetes; Approved Standard-Second Edition. CLSI document M24-A2. Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, PA 19087 USA, 2011. 7. Clinical and Laboratory Standards Institute. Methods for Antimicrobial Susceptibility Testing for Human Mycoplasmas; Approved Guideline. CLSI document M43-A. Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, PA 19087 USA, 2011. a) Friedman JM and Polifka JE. Teratogenic Effects of Drugs. A Resource for Clinicians (TERIS). Baltimore, MD: The Johns Hopkins University Press, 2000: 149-195. b) Cziezel AE and Rockenbauer M. Teratogenic study of doxycycline. Obstet Gynecol 1997; 89: 524-528. c) Horne HW Jr and Kundsin RB. The role of mycoplasma among 81 consecutive pregnancies: a prospective study. Int J Fertil 1980; 25: 315-317. d) Hale T. Medications and Mothers Milk. 9th edition. Amarillo, TX: Pharmasoft Publishing, 2000:225-226.

This product's label may have been updated. For current full prescribing information, please call 845-232-1683.

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Chartwell Governmental & Specialty RX LLC
Congers, NY 10920

Rev 01 6/2014

NDC 68999-417-01

DOXYCYCLINE
for Oral Suspension USP

25 mg/5 mL*

When reconstituted as directed,
each teaspoonful (5 mL) contains doxycycline
monohydrate equivalent to 25 mg of doxycycline.

RASPBERRY FLAVORED

60 mL (when reconstituted) Rx only

Chartwell RX
GOVERNMENTAL & SPECIALTY

DOXYCYCLINE  doxycycline powder, for suspension

Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:68999-417 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength DOXYCYCLINE (DOXYCYCLINE ANHYDROUS) DOXYCYCLINE ANHYDROUS 25 mg  in 5 mL

Inactive Ingredients Ingredient Name Strength SUCROSE   D&C RED NO. 27   ALUMINUM OXIDE   ETHYL ACETATE   MALTODEXTRIN   METHYLPARABEN   PROPYLPARABEN

Product Characteristics Color PINK Score      Shape Size Flavor RASPBERRY Imprint Code Contains

Packaging # Item Code Package Description 1 NDC:68999-417-01 60 mL in 1 BOTTLE, GLASS

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA065454 07/16/2008

Labeler - CHARTWELL GOVERNMENTAL & SPECIALTY RX LLC (079394070)

Revised: 08/2017   CHARTWELL GOVERNMENTAL & SPECIALTY RX LLC

DOXYCYCLINE (dox i SYE kleen) is a tetracycline antibiotic. It kills certain bacteria or stops their growth. It is used to treat many kinds of infections, like dental, skin, respiratory, and urinary tract infections. It also treats acne, Lyme disease, malaria, and certain sexually transmitted infections.

This drug also comes in other forms, including Oral capsule, Topical pad, Oral tablet, Injectable solution

This drug can cause serious side effects. See which side effects you should report to your doctor right away.

Know how to use your medication, and learn what might happen if you miss a dose.

Talk to your healthcare provider if you have any of these conditions.

Know what to watch for and get tips for reducing your risks while taking this drug.