Adoxa

Name: Adoxa

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Reviewed on 7/28/2016 References Reference: FDA Prescribing Information

Description

Doxycycline is a broad-spectrum antibiotic synthetically derived from oxytetracycline. Doxycycline 150 mg capsules contain doxycycline monohydrate equivalent to 150 mg of doxycycline for oral administration. Inactive ingredients include colloidal silicon dioxide, FD&C Red #40, FD&C Yellow #6, gelatin, magnesium stearate, microcrystalline cellulose, sodium starch glycolate, and titanium dioxide. Its molecular weight is 462.46. The chemical designation of the light-yellow crystalline powder is alpha-6-deoxy-5-oxytetracycline.

Structural formula:


C22H24N2O8•H2O

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.

How supplied

Doxycycline Capsules 150 mg have a peach opaque cap printed “ADOXA®” in black ink/peach opaque body printed “150 mg” in black ink. Each capsule contains doxycycline monohydrate equivalent to 150 mg of doxycycline. They are supplied as follows:

Bottle of 60 NDC 10337-815-06

Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.]

DISPENSE IN A TIGHT LIGHT RESISTANT CONTAINER AS DEFINED IN THE USP/NF.

Manufactured by: PharmaDerm, A division of Fougera Pharmaceuticals Inc., Melville, NY 11747 USA. Manufactured by: PAR PHARMACEUTICAL COMPANIES, INC., Spring Valley, NY 10977 USA, IL221C. Revised: May 2013

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 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.

Microbiology

The tetracyclines are primarily bacteriostatic and are thought to exert their antimicrobial effect by the inhibition of protein synthesis. The tetracyclines, including doxycycline, have a similar antimicrobial spectrum of activity against a wide range of gram-positive and gramnegative microorganisms. Cross-resistance of these microorganisms to tetracyclines is common.

Doxycycline has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section.

Aerobic Gram-Positive Microorganisms

Because many strains of the following groups of gram-positive microorganisms have been shown to be resistant to tetracyclines, culture and susceptibility testing are recommended:

Bacillus anthracis
Listeria monocytogenes

Staphylococcus aureus*

*Doxycycline is not the drug of choice in the treatment of any type of staphylococcal infection.

Up to 44 percent of strains of Streptococcus pyogenes and 74 percent of Streptococcus faecalis have been found to be resistant to tetracycline drugs. Therefore, tetracyclines should not be used to treat streptococcal infections unless the microorganism has been demonstrated to be susceptible.

Streptococcus pneumoniae

Aerobic Gram-Negative Microorganisms

Bartonella bacilliformis
Brucella species

Calymmatobacterium granulomatis

Campylobacter fetus

Francisella tularensis

Haemophilus ducreyi

Haemophilus influenzae

Neisseria gonorrhoeae

Vibrio cholerae

Yersinia pestis

Because many strains of the following groups of gram-negative microorganisms have been shown to be resistant to tetracyclines, culture and susceptibility testing are recommended:

Acinetobacter species
Enterobacter aerogenes

Escherichia coli

Klebsiella species

Shigella species

Anaerobic Microorganisms

Actinomyces israelii
Clostridium species

Fusobacterium fusiforme

Other Microorganisms

Borrelia recurrentis
Chlamydia psittaci

Chlamydia trachomatis

Mycoplasma pneumoniae

Rickettsiae

Treponema pallidum

Treponema pertenue

Susceptibility Tests

Dilution Techniques

Quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (MIC's). These MIC's provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MIC's should be determined using a standardized procedure. Standardized procedures are based on a dilution method1,3 (broth or agar) or equivalent with standardized inoculum concentrations and standardized concentrations of tetracycline powder. The MIC values should be interpreted according to the following criteria for indicated aerobic microorganisms other than Haemophilus species, Neisseria gonorrhoeae, and Streptococcus pneumoniae:

MIC (mcg/mL) Interpretation
≤ 4 Susceptible (S)
8 Intermediate (I)
> 16 Resistant (R)
When testing Haemophilus spp.a
MIC (mcg/mL) Interpretation
≤ 2 Susceptible (S)
4 Intermediate (I)
> 8 Resistant (R)
When testing Neisseria gonorrhoeaeb
MIC (mcg/mL) Interpretation
≤ 0.25 Susceptible (S)
0.5-1 Intermediate (I)
≥ 2 Resistant (R)
When testing Streptococcus pneumoniaec
MIC (mcg/mL) Interpretation
≤ 2 Susceptible (S)
4 Intermediate (I)
≥ 8 Resistant (R)
a Interpretative criteria applicable only to tests performed by broth microdilution method using Haemophilus Test Medium (HTM).1,3
b Interpretative criteria applicable only to tests performed by agar dilution method using GC agar base with 1% defined growth supplement.1,3
c Interpretative criteria applicable only to tests performed by broth microdilution method using cationadjusted Mueller-Hinton broth with 2 to 5% lysed horse blood.1,3

A report of “Susceptible” indicates that the pathogen is likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable. A report of “Intermediate” 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 is physiologically concentrated or in situations where high dosage of drug can be used. This category also provides a buffer zone which prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of “Resistant” indicates that the pathogen is not likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable; other therapy should be selected.

Standardized susceptibility test procedures require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures. Standard tetracycline powder should provide the following MIC values:

Microorganism   MIC (mcg/mL)
Enterococcus faecalis ATCC 29212 8-32
Escherichia coli ATCC 25922 0.5-2
Haemophilus influenzaea ATCC 49247 4-32
Neisseria gonorrhoeaeb ATCC 49226 0.25-1
Pseudomonas aeruginosa ATCC 27853 8-32
Staphylococcus aureus ATCC 29213 0.12-1
Streptococcus pneumoniaec ATCC 49619 0.12-0.5
a Range applicable only to tests performed by broth microdilution method using Haemophilus Test Medium(HTM).1,3
b Range applicable only to tests performed by agar dilution method using GC agar base with 1% defined growth supplement. 1,3
c Range applicable only to tests performed by broth microdilution method using cation-adjusted Mueller- Hinton broth with 2 to 5% lysed horse blood. 1,3

Diffusion Techniques

Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure requires the use of standardized inoculum concentrations. This procedure uses paper disks impregnated with 30 mcg tetracycline or 30 mcg doxycycline to test the susceptibility of microorganisms to doxycycline.

Reports from the laboratory providing results of the standard single-disk susceptibility test with 30 mcg tetracycline-class disk or the 30 mcg doxycycline disk should be interpreted according to the following criteria for indicated aerobic microorganisms other than Haemophilus species, Neisseria gonorrhoeae, and Streptococcus pneumoniae:

Zone Diameter (mm) Interpretation
Tetracycline Doxycycline
≥ 15 ≥ 14 Susceptible (S)
12-14 11-13 Intermediate (I)
≤ 11 ≤ 10 Resistant (R)
When testing Haemophilus spp.a
Zone Diameter (mm) Interpretation
tetracycline  
≥ 29 Susceptible (S)
26-28 Intermediate (I)
≤ 25 Resistant (R)
When testing Neisseria gonorrhoeaeb
Zone Diameter (mm) Interpretation
tetracycline  
≥ 38 Susceptible (S)
31-37 Intermediate (I)
≤ 30 Resistant (R)

Zone diameters ≤ 19 mm may indicate a plasmid-mediated tetracycline-resistant Neisseria gonorrhoeae (TRNG) isolate. These TRNG strains should be confirmed by the dilution test (MIC ≥ 16 mcg/mL).

When testing Streptococcus pneumoniac

Zone Diameter (mm) Interpretation
tetracycline  
≥ 23 Susceptible (S)
19-22 Intermediate (I)
≤ 18 Resistant (R)

a Interpretative criteria applicable only to tests performed by disk diffusion method using a 30 mcg tetracycline-class disk and using Haemophilus Test Medium (HTM).
b Interpretative criteria applicable only to tests performed by disk diffusion method using a 30 mcg tetracycline-class disk and using GC agar base with 1% defined growth supplement.
c Interpretative criteria applicable only to tests performed by disk diffusion method using a 30 mcg tetracycline-class disk and using Mueller-Hinton agar with 5% defibrinated sheep blood and incubated with 5% CO2.2,3

Interpretation should be as stated above for results using dilution techniques. Interpretation involves correlation of the diameter obtained in the disk test with the MIC for tetracycline or doxycycline, respectively.

As with standardized dilution techniques, diffusion methods require the use of laboratory control microorganisms that are used to control the technical aspects of the laboratory procedures. For the diffusion technique, the 30 mcg tetracycline-class disk or the 30 mcg doxycycline disk should provide the following zone diameters in these laboratory test quality control strains:

Microorganism   Zone Diameter (mm)
tetracycline doxycycline
Escherichia coli ATCC 25922 18-25 18-24
Haemophilus influenzaea ATCC 49247 14-22 ---
Neisseria gonorrhoeaeb ATCC 49226 30-42
Staphylococcus aureus ATCC 25923 24-30 23-29
Streptococcus pneumoniaec ATCC 49619 27-31 ---
a Range applicable only to tests performed by disk diffusion method using a 30 mcg tetracycline-class disk and using Haemophilus Test Medium (HTM). 2,3
b Range applicable only to tests performed by disk diffusion method using a 30 mcg tetracycline-class disk and using GC agar base with 1% defined growth supplement. 2,3
c Range applicable only to tests performed by disk diffusion method using a 30 mcg tetracycline-class disk and using Mueller-Hinton agar with 5% defibrinated sheep blood and incubated with 5% CO2.2,3

Anaerobic Techniques

For anaerobic bacteria, the susceptibility to tetracycline as MIC's can be determined by standardized test methods.4 The MIC values obtained should be interpreted according to the following criteria:

MIC (mcg/mL) Interpretation
> 4 Susceptible (S)
8 Intermediate (I)
< 16 Resistant (R)

Interpretation is identical to that stated above for results using dilution techniques.

As with other susceptibility techniques, the use of laboratory control microorganisms is required to control the technical aspects of the laboratory standardized procedures. Standardized tetracycline powder should provide the following MIC values:

Microorganism   MIC (mcg/mL)
Bacteroides fragilisa ATCC 25285 0.12-0.5
Bacteroides thetaiotaomicrona ATCC 29741 8-32
a Range applicable only to tests performed by the reference agar dilution method.

Animal Pharmacology And Animal Toxicology

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.

REFERENCES

1. M7-A7. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; Approved standard - 7th edition. Clinical and Laboratory Standards Institute (Formerly NCCLS), Wayne, PA; 2006

2. M2-A9. Performance standards for antimicrobial disk susceptibility Tests; Approved standard - 9th edition. Clinical and Laboratory Standards Institute (Formerly NCCLS), Wayne, PA; 2006.

3. M100-S17. Performance standards for antimicrobial susceptibility testing; 17th informational supplement. Clinical and Laboratory Standards Institute (Formerly NCCLS), Wayne, PA; 2007.

4. M11-A7. Methods for antimicrobial susceptibility testing of anaerobic bacteria; Approved standard - 7th edition.Clinical and Laboratory Standards Institute (Formerly NCCLS), Wayne, PA; 2007.

How should I take Adoxa (doxycycline)?

Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Take doxycycline with a full glass of water. Drink plenty of liquids while you are taking doxycycline.

Most brands of doxycyline may be taken with food or milk if the medicine upsets your stomach. Different brands of doxycycline may have different instructions about taking them with or without food.

Take Oracea on an empty stomach, at least 1 hour before or 2 hours after a meal.

You may open a Doryx capsule or break up a Doryx tablet and sprinkle the medicine into a spoonful of applesauce to make swallowing easier. Swallow right away without chewing. Do not save the mixture for later use. Drink a full glass (8 ounces) of cool water right away.

Do not crush, break, or open a delayed-release capsule or tablet. Swallow the pill whole.

You may need to split the Acticlate tablet to get the correct dose. The tablet is scored so you can break it apart easily.

Measure liquid medicine with the dosing syringe provided, or with a special dose-measuring spoon or medicine cup. If you do not have a dose-measuring device, ask your pharmacist for one.

If you take doxycycline to prevent malaria: Start taking the medicine 1 or 2 days before entering an area where malaria is common. Continue taking the medicine every day during your stay and for at least 4 weeks after you leave the area. Use protective clothing, insect repellents, and mosquito netting around your bed to further prevent mosquito bites that could cause malaria.

Use this medicine for the full prescribed length of time. Your symptoms may improve before the infection is completely cleared. Skipping doses may also increase your risk of further infection that is resistant to antibiotics. Doxycycline will not treat a viral infection such as the flu or a common cold.

If you need surgery, tell the surgeon ahead of time that you are using doxycycline.

Store at room temperature away from moisture, heat, and light.

Throw away any unused medicine after the expiration date on the label has passed. Using expired doxycycline can cause damage to your kidneys.

Commonly used brand name(s)

In the U.S.

  • Adoxa
  • Adoxa CK
  • Adoxa Pak
  • Adoxa TT
  • Doryx
  • Doryx MPC
  • Monodox
  • Oracea
  • Periostat
  • Vibramycin Calcium
  • Vibramycin Hyclate
  • Vibra-Tabs

Available Dosage Forms:

  • Tablet
  • Powder for Suspension
  • Capsule
  • Capsule, Extended Release
  • Tablet, Delayed Release
  • Capsule, Delayed Release
  • Syrup

Therapeutic Class: Antibiotic

Chemical Class: Tetracycline (class)

Adoxa Side Effects

Along with its needed effects, a medicine 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:

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 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

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Uses of Adoxa

  • It is used to treat pimples (acne).
  • It is used to treat or prevent bacterial infections.
  • It is used to prevent malaria.
  • It is used to treat swelling of the tissue around the teeth (periodontitis). It is used with scaling and root planing.
  • It may be given to you for other reasons. Talk with the doctor.

What do I need to tell my doctor BEFORE I take Adoxa?

  • If you have an allergy to doxycycline or any other part of Adoxa (doxycycline tablets and capsules).
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you are taking any of these drugs: Acitretin, isotretinoin, or a penicillin.
  • If you are breast-feeding or plan to breast-feed.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take Adoxa with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

Overdosage

In case of overdosage, discontinue medication, treat symptomatically and institute supportive measures. Dialysis does not alter serum half-life, and it would not be of benefit in treating cases of overdosage.

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