NicAzel Doxy Kit

Name: NicAzel Doxy Kit

NicAzel DoxyKit

Rx Only

Contains:

1 Bottle Doxycycline Tablets (30 count, 100 mg each)

1 Bottle Nicazel®FORTE Tablets (60 count)

Clinical pharmacology

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

1.0

1.5

2.0

3.0

4.0

8.0

12.0

24.0

48.0

72.0

Conc. (mcg/mL):

1.02

2.26

2.67

3.01

3.16

3.03

2.03

1.62

0.95

0.37

0.15

Average Observed Values

Maximum Concentration

3.61 mcg/mL (± 0.9 sd)

Time of Maximum Concentration

2.60 hr (± 1.10 sd)

Elimination Rate Constant

0.049 per hr (± 0.030 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 1-5%/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.

MICROBIOLOGY:

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. 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 tablets.

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 Actinomyces species
Borrelia recurrentis
Chlamydophila psittaci
Chlamydia trachomatis
Mycoplasma pneumoniae
Rickettsiae
Treponema pallidum
Treponema pertenue
Ureaplasma urealyticum

Parasites

Balantidium coli
Entamoeba species

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 (broth and/or agar).1,2,4 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 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.5 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 per mL)

Zone Diameter (mm)

Agar Dilution

(mcg per mL)

S

I

R

S

I

R

S

I

R

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

-

-

Neisseria gonorrhoeae‡

Tetracycline

-

-

-

≥38

31-37

≤30

≤0.25

0.5-1

≥2

Norcardiae and other aerobic Actinomyces species†

Doxycycline

≤1

2-4

≥8

-

-

-

-

-

-

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

* 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 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 test.1,2,3,4,5,6,7

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 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 per mL)

Zone Diameter

(mm)

Agar Dilution

(mcg per 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

-

-

0.125-0.5

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

NicAzel Doxy Kit Dosage and Administration

THE USUAL DOSAGE AND FREQUENCY OF ADMINISTRATION OF DOXYCYCLINE DIFFERS FROM THAT OF THE OTHER TETRACYCLINES. EXCEEDING THE RECOMMENDED DOSAGE MAY RESULT IN AN INCREASED INCIDENCE OF SIDE EFFECTS.

Adults: The usual dose of oral doxycycline is 200 mg on the first day of treatment (administered 100 mg every 12 hours or 50 mg every 6 hours) followed by a maintenance dose of 100 mg/day. The maintenance dose may be administered as a single dose or as 50 mg every 12 hours. In the management of more severe infections (particularly chronic infections of the urinary tract), 100 mg every 12 hours is recommended.

For pediatric patients above eight years of age: The recommended dosage schedule for pediatric patients weighing 100 pounds or less is 2 mg/lb of body weight divided into two doses on the first day of treatment, followed by 1 mg/lb of body weight given as a single daily dose or divided into two doses, on subsequent days. For more severe infections up to 2 mg/lb of body weight may be used. For pediatric patients over 100 pounds the usual adult dose should be used.

Uncomplicated gonococcal infections in adults (except anorectal infections in men): 100 mg, by mouth, twice a day for 7 days. As an alternate single visit dose, administer 300 mg stat followed in one hour by a second 300 mg dose.

Acute epididymo-orchitis caused by N. gonorrhoeae: 100 mg, by mouth, twice a day for at least 10 days.

Primary and secondary syphilis: 300 mg a day in divided doses for at least 10 days.

Uncomplicated urethral, endocervical, or rectal infection in adults caused by Chlamydia trachomatis: 100 mg, by mouth, twice a day for at least 7 days.

Nongonococcal urethritis caused by C. trachomatis and U. urealyticum: 100 mg, by mouth, twice a day for at least 7 days.

Acute epididymo-orchitis caused by C. trachomatis: 100 mg, by mouth, twice a day for at least 10 days.

Inhalational anthrax (post-exposure):
ADULTS: 100 mg of doxycycline, by mouth, twice a day for 60 days.
CHILDREN: weighing less than 100 pounds (45 kg); 1 mg/lb (2.2 mg/kg) of body weight, by mouth, twice a day for 60 days. Children weighing 100 pounds or more should receive the adult dose.

When used in streptococcal infections, therapy should be continued for 10 days.

Administration of adequate amounts of fluid along with capsule and tablet forms of drugs in the tetracycline class is recommended to wash down the drugs and reduce the risk of esophageal irritation and ulceration. (See ADVERSE REACTIONS.) If gastric irritation occurs, doxycycline may be given with food. Ingestion of a high fat meal has been shown to delay the time to peak plasma concentrations by an average of one hour and 20 minutes. However, in the same study, food enhanced the average peak concentration by 7.5% and the area under the curve by 5.7%.

References

1. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing; Twenty-third Informational Supplement, CLSI document M100-S23. CLSI document M100S23, Clinical 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 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-A11, Clinical 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 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 Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne Pennsylvania 19087, USA, 2012.
6. Clinical and Laboratory Standards Institute (CLSI). Methods for Mycobacteria, Nocardiae, and Other Aerobic Actinomycetes; Approved Standard – Second Edition. CLSI document M24-A2, Clinical Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne Pennsylvania 19087, USA, 2011.
7. Clinical and Laboratory Standards Institute (CLSI). Methods for Antimicrobial Susceptibility Testing for Human Mycoplasmas; Approved Guideline. CLSI document M43-A, Clinical Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne Pennsylvania 19087, USA, 2011.
8. Friedman JM and Polifka JE. Teratogenic Effects of Drugs. A Resource for Clinicians (TERIS). Baltimore, MD: The Johns Hopkins University Press: 2000: 149-195.
9. Cziezel AE and Rockenbauer M. Teratogenic study of doxycycline. Obstet Gynecol 1997;89:524-528.
10. Horne HW Jr. and Kundsin RB. The role of mycoplasma among 81 consecutive pregnancies: a prospective study. Int J Fertil 1980; 25:315-317.
11. Hale T. Medications and Mothers Milk. 9th edition. Amarillo, TX: Pharmasoft Publishing 2000; 225-226.

Manufactured For:
Elorac, Inc.
Vernon Hills, IL 60061

Made in the USA

Revised: 03/14, Revision 1

10-303

1338-30

DOXYCYCLINE TABLETS

Rx Only

For the Consumer

Applies to doxycycline: oral capsule, oral capsule delayed release, oral capsule extended release, oral powder for suspension, oral syrup, oral tablet, oral tablet delayed release

Along with its needed effects, doxycycline (the active ingredient contained in NicAzel Doxy) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking doxycycline:

Incidence not known
  • Bloating
  • chills
  • clay-colored stools
  • constipation
  • cough
  • dark urine
  • decreased appetite
  • diarrhea
  • diarrhea, watery and severe, which may also be bloody
  • difficulty with swallowing
  • dizziness
  • fast heartbeat
  • feeling of discomfort
  • fever
  • headache
  • hives, itching, puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
  • hives or welts, itching, or rash
  • increased thirst
  • indigestion
  • inflammation of the joints
  • joint or muscle pain
  • large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
  • loss of appetite
  • nausea and vomiting
  • numbness or tingling of the face, hands, or feet
  • pain in the stomach, side, or abdomen, possibly radiating to the back
  • redness and soreness of the eyes
  • redness of the skin
  • sore throat
  • sores in the mouth
  • stomach cramps
  • stomach pain or tenderness
  • swelling of the feet or lower legs
  • swollen lymph glands
  • tightness in the chest
  • unusual tiredness or weakness
  • unusual weight loss
  • yellow eyes or skin

Some side effects of doxycycline may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Incidence not known
  • Back, leg, or stomach pains
  • black, tarry stools
  • bleeding gums
  • blood in the urine or stools
  • blurred vision
  • bulging soft spot on the head of an infant
  • change in the ability to see colors, especially blue or yellow
  • chest pain, discomfort, or burning
  • cracks in the skin
  • decrease in vision
  • difficulty breathing
  • discoloration of the thyroid glands
  • double vision
  • general body swelling
  • heartburn
  • increased sensitivity of the skin to sunlight
  • loss of heat from the body
  • lower back or side pain
  • nosebleeds
  • pain or burning in the throat
  • pain with swallowing
  • painful or difficult urination
  • pale skin
  • pinpoint red spots on the skin
  • rash with flat lesions or small raised lesions on the skin
  • red, swollen skin
  • redness or other discoloration of the skin
  • redness, swelling, or soreness of the tongue
  • scaly skin
  • severe nausea
  • severe stomach pain
  • severe sunburn
  • sores, ulcers, or white spots on the lips or tongue or inside the mouth
  • unusual bleeding or bruising
  • vomiting blood

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