Halosin

Halosin may be available in the countries listed below.

Ingredient matches for Halosin

Halothane

Halothane is reported as an ingredient of Halosin in the following countries:

• Bangladesh

International Drug Name Search

Detraine

Detraine may be available in the countries listed below.

Ingredient matches for Detraine

Hydrocortisone

Hydrocortisone is reported as an ingredient of Detraine in the following countries:

• Spain

Propanocaine

Propanocaine hydrochloride (a derivative of Propanocaine) is reported as an ingredient of Detraine in the following countries:

• Spain

International Drug Name Search

Lisocard

Lisocard may be available in the countries listed below.

Ingredient matches for Lisocard

Lisinopril

Lisinopril dihydrate (a derivative of Lisinopril) is reported as an ingredient of Lisocard in the following countries:

• Bahrain


• Iraq


• Lebanon


• Libya


• Nigeria


• Oman


• Saudi Arabia


• Sudan


• United Arab Emirates


• Yemen

International Drug Name Search

Sandoz Minocycline

Sandoz Minocycline may be available in the countries listed below.

Ingredient matches for Sandoz Minocycline

Minocycline

Minocycline hydrochloride (a derivative of Minocycline) is reported as an ingredient of Sandoz Minocycline in the following countries:

• Canada

International Drug Name Search

bromfenac ophthalmic

Generic Name: bromfenac (ophthalmic) (BROM fen ak)

Brand names: Xibrom, Bromday

What is bromfenac ophthalmic?

Bromfenac ophthalmic is a non-steroidal anti-inflammatory drug (NSAID).

Bromfenac ophthalmic is used to treat swelling and pain caused by cataract surgery.

Bromfenac ophthalmic may also be used for other purposes not listed here.

What is the most important information I should know about bromfenac ophthalmic

Use this medication exactly as it was prescribed for you. Do not use it in larger doses or for longer than recommended by your doctor. Follow the directions on your prescription label.

Before using this medication, tell your doctor if you are pregnant or breast-feeding.

If you miss a dose, use the medication as soon as you remember. If it is almost time for the next dose, skip the missed dose and wait until your next regularly scheduled dose. Do not use extra medicine to make up the missed dose.

Before using bromfenac tell your doctor if you are using a steroid such as prednisone, dexamethasone, or others. You may not be able to use bromfenac ophthalmic or you may need dosage adjustments or special tests during treatment.

Stop using this medication and get emergency medical help if you think you have used too much medicine, or if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Less serious side effects are more likely, and you may have none at all. Talk to your doctor about any side effect that seems unusual or is especially bothersome.

What should I discuss with my healthcare provider before using bromfenac ophthalmic?

You should not use this medication if you have ever had an allergic reaction to bromfenac.

Before using bromfenac ophthalmic, tell your doctor if you are allergic to any drugs, or if you have:

• 
  

  asthma;

  
  


• 
  

  diabetes;

  
  


• 
  

  rheumatoid arthritis;

  
  


• 
  

  dry eye syndrome;

  
  


• 
  

  a drug allergy;

  
  


• 
  

  a bleeding disorder; or

  
  


• 
  

  more than one eye surgery in a short period of time.

  
  

If you have any of these conditions, you may need a dose adjustment or special tests to safely use bromfenac ophthalmic.

FDA pregnancy category C: This medication may be harmful to an unborn baby. Do not use bromfenac without telling your doctor if you are pregnant. Tell your doctor if you become pregnant during treatment. It is not known if bromfenac ophthalmic passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

How should I use bromfenac ophthalmic?

Use bromfenac ophthalmic exactly as it was prescribed for you. Do not use it in larger doses or for longer than recommended by your doctor. Follow the directions on your prescription label.

Wash your hands before using the eye drops.

If you wear contact lenses, remove them before applying bromfenac ophthalmic. Ask your doctor if contact lenses can be reinserted after putting in the eye drops. Bromfenac ophthalmic may contain a preservative (benzalkonium chloride) that can cause discoloration of contact lenses.

To apply the eye drops:

• 
  

  Tilt your head back slightly and pull down on the lower eyelid to create a small pocket. Hold the dropper above the eye with the dropper tip down. Look up and away from the dropper. Squeeze out a drop and close your eye. Gently press your finger to the inside corner of the eye (near the nose) for about 1 minute to keep the liquid from draining into your tear duct. If you use more than one drop in the same eye, wait about 5 minutes before putting in the next drop.

  
  

Bromfenac ophthalmic is usually used two times a day for 14 days. Follow your doctor's directions.

Do not touch the dropper to any surface, including the eyes or hands. If the dropper becomes contaminated, it could cause an infection in your eye. Store the drops at room temperature away from heat and moisture. Keep the bottle tightly closed when not in use.

What happens if I miss a dose?

Use the medication as soon as you remember. If it is almost time for the next dose, skip the missed dose and wait until your next regularly scheduled dose. Do not use extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention if you think you have used too much of this medicine, or if anyone has accidentally swallowed it. An overdose of this medication is unlikely to be harmful.

What should I avoid while taking bromfenac ophthalmic?

Bromfenac ophthalmic can cause side effects that may impair your vision. Be careful if you drive or do anything that requires you to be able to see clearly. Avoid using other medications in your eyes during treatment with bromfenac ophthalmic unless your doctor has told you to.

Bromfenac ophthalmic side effects

Stop using bromfenac ophthalmic and get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Stop using bromfenac ophthalmic and call your doctor at once if you have any change in your vision.

Other less serious side effects are more likely to occur, such as:

• 
  

  feeling like something is in your eye;

  
  


• 
  

  eye pain, itching, or redness; or

  
  


• 
  

  headache.

  
  

This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.

Bromfenac Dosing Information

Usual Adult Dose for Postoperative Ocular Inflammation:

For the treatment of postoperative inflammation and the reduction of ocular pain in patients who have undergone cataract extraction:
Instill 1 drop in affected eye(s) 2 times a day beginning 24 hours after cataract surgery and continuing throughout the first 2 weeks of the postoperative period.

Bromday (bromfenac ophthalmic solution 0.09%) for the treatment of postoperative inflammation and reduction of ocular pain in patients who have undergone cataract surgery:
one drop applied to the affected eye(s) once daily beginning 1 day prior to cataract surgery, continued on the day of surgery, and through the first 14 days of the postoperative period.

Bromfenac ophthalmic, like most topical nonsteroidal anti-inflammatory agents may increase the risk for the occurrence and severity of corneal adverse events if instilled more than 24 hours prior to and longer than 2 weeks following cataract surgery.

What other drugs will affect bromfenac ophthalmic?

Before using bromfenac tell your doctor if you are using a steroid such as prednisone, dexamethasone, and others.

This list is not complete and there may be other drugs that can interact with bromfenac ophthalmic Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

More bromfenac resources

• Bromfenac Dosage
• Bromfenac Use in Pregnancy & Breastfeeding
• Bromfenac Drug Interactions
• Bromfenac Support Group
• 0 Reviews for Bromfenac - Add your own review/rating

• Bromday Prescribing Information (FDA)


• Bromday Consumer Overview


• Bromday Advanced Consumer (Micromedex) - Includes Dosage Information


• Bromday MedFacts Consumer Leaflet (Wolters Kluwer)


• Xibrom Prescribing Information (FDA)


• Xibrom Monograph (AHFS DI)


• Xibrom Consumer Overview

Compare bromfenac with other medications

• Postoperative Ocular Inflammation

Where can I get more information?

• Your pharmacist can provide more information about bromfenac ophthalmic.

Mycophenolic Acid

In the US, Mycophenolic Acid (mycophenolic acid systemic) is a member of the drug class selective immunosuppressants and is used to treat Dermatomyositis and Rejection Prophylaxis.

US matches:

• Mycophenolic Acid Delayed-Release Tablets


• Mycophenolic acid

Scheme

Rec.INN

ATC (Anatomical Therapeutic Chemical Classification)

L04AA06

CAS registry number (Chemical Abstracts Service)

0024280-93-1

Chemical Formula

C17-H20-O6

Molecular Weight

320

Therapeutic Categories

Antineoplastic antibacterial

Selective immunosuppressant

Chemical Name

4-Hexenoic acid, 6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methyl-3-oxo-5-isobenzofuranyl)-4-methyl-, (E)-

Foreign Names

• Acidum Mycophenolicum (Latin)
• Mycophenolsäure (German)
• Acide mycophénolique (French)
• Acido micofenolico (Spanish)

Generic Names

• Acide Mycophénolique (OS: DCF)
• Mycophenolic Acid (OS: BAN, USAN)
• Acidum mycophenolicum (IS)
• Lilly 68618 (IS: Lilly)
• MPA (IS)
• NSC 129185 (IS)
• Mycophenolate Mofetil (OS: USAN, BANM)
• ME-MPA (IS: Syntex)
• RS 61443 (IS: Syntex)
• Myclophenolas mofetil (PH: Ph. Eur. 6)
• Mycophenolate Mofetil (PH: BP 2010, Ph. Eur. 6, USP 32)
• Mycophenolic acid monosodium salt (IS)
• Mycophenolic monosodium salt (IS)
• Myxophenolic acid, sodium salt (IS)

Brand Names

• Mofetilmikofenolat Teva
  Teva, Slovenia



• Myfenax
  Teva, Slovenia



• Myfortic
  Novartis, South Africa



• Baxmune
  Ranbaxy, India



• Cellcept
  Chugai, Japan; Roche, United Arab Emirates; Roche, Argentina; Roche, Austria; Roche, Australia; Roche, Aruba; Roche, Bosnia & Herzegowina; Roche, Bangladesh; Roche, Belgium; Roche, Bahrain; Roche, Brazil; Roche, Botswana; Roche, Belarus; Roche, Canada; Roche, Switzerland; Roche, Chile; Roche, China; Roche, Colombia; Roche, Cuba; Roche, Cyprus; Roche, Czech Republic; Roche, Germany; Roche, Denmark; Roche, Ecuador; Roche, Estonia; Roche, Egypt; Roche, Spain; Roche, Finland; Roche, France; Roche, United Kingdom; Roche, Georgia; Roche, Ghana; Roche, Greece; Roche, Hong Kong; Roche, Croatia (Hrvatska); Roche, Hungary; Roche, Indonesia; Roche, Ireland; Roche, Israel; Roche, India; Roche, Iraq; Roche, Iran; Roche, Iceland; Roche, Italy; Roche, Jamaica; Roche, Jordan; Roche, Kenya; Roche, South Korea; Roche, Kuwait; Roche, Kazakhstan; Roche, Lebanon; Roche, Sri Lanka; Roche, Lithuania; Roche, Luxembourg; Roche, Morocco; Roche, Macedonia; Roche, Mauritius; Roche, Malawi; Roche, Mexico; Roche, Malaysia; Roche, Namibia; Roche, Nigeria; Roche, Netherlands; Roche, Norway; Roche, Nepal; Roche, New Zealand; Roche, Oman; Roche, Peru; Roche, Philippines; Roche, Pakistan; Roche, Poland; Roche, Portugal; Roche, Qatar; Roche, Romania; Roche, Serbia; Roche, Russian Federation; Roche, Saudi Arabia; Roche, Sudan; Roche, Singapore; Roche, Slovenia; Roche, Slovakia; Roche, Syria; Roche, Thailand; Roche, Tunisia; Roche, Turkey; Roche, Trinidad & Tobago; Roche, Taiwan; Roche, Tanzania; Roche, Ukraine; Roche, Uganda; Roche, United States; Roche, Uruguay; Roche, Uzbekistan; Roche, Venezuela; Roche, Vietnam; Roche, South Africa; Roche, Zambia; Roche, Zimbabwe; Roche Diagnostic, Algeria



• CellCept
  Roche, Sweden



• Linfonex
  Farmindustria, Peru; Recalcine, Ecuador; Tadt, Chile



• MMF
  Medis, Tunisia



• Mycocell
  Biotoscana, Colombia



• Mycophenolate Mofetil Sandoz
  Sandoz, Switzerland; Sandoz, Estonia; Sandoz, Latvia



• Mycophenolate Mofetil
  Accord, United States; Apotex, United States; Endo, United States; Mylan, United States; Roxane, United States; Sandoz, United States; Teva USA, United States; Zydus, United States



• Myfenax
  Teva Pharma, Switzerland



• Myfetil
  Specifar, Greece



• Mykofenolat Mofetil Sandoz
  Sandoz, Slovakia



• Trixin
  Pliva, Croatia (Hrvatska)



• Myfortic
  Dr. Fisher, Netherlands; EU-Pharma, Netherlands; Euro, Netherlands; Medcor, Netherlands; Novartis, Austria; Novartis, Australia; Novartis, Belgium; Novartis, Brazil; Novartis, Canada; Novartis, Switzerland; Novartis, Chile; Novartis, Colombia; Novartis, Czech Republic; Novartis, Germany; Novartis, Denmark; Novartis, Ecuador; Novartis, Estonia; Novartis, Spain; Novartis, Finland; Novartis, France; Novartis, United Kingdom; Novartis, Greece; Novartis, Hong Kong; Novartis, Croatia (Hrvatska); Novartis, Hungary; Novartis, Indonesia; Novartis, Ireland; Novartis, Israel; Novartis, Iceland; Novartis, Italy; Novartis, Lithuania; Novartis, Luxembourg; Novartis, Latvia; Novartis, Malta; Novartis, Mexico; Novartis, Malaysia; Novartis, Netherlands; Novartis, Norway; Novartis, Oman; Novartis, Philippines; Novartis, Poland; Novartis, Portugal; Novartis, Romania; Novartis, Serbia; Novartis, Russian Federation; Novartis, Sweden; Novartis, Singapore; Novartis, Slovenia; Novartis, Slovakia; Novartis, Thailand; Novartis, Turkey; Novartis, Taiwan; Novartis, United States; Novartis, Venezuela; Novartis, Vietnam

International Drug Name Search

Glossary

BAN	British Approved Name
BANM	British Approved Name (Modified)
DCF	Dénomination Commune Française
IS	Inofficial Synonym
OS	Official Synonym
PH	Pharmacopoeia Name
Rec.INN	Recommended International Nonproprietary Name (World Health Organization)
USAN	United States Adopted Name

Click for further information on drug naming conventions and International Nonproprietary Names.

Doxycycline Monohydrate

Doxycycline Monohydrate Capsules

Revised: January 2012

Rx only

191157-4

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Doxycycline Monohydrate Capsules and other antibacterial drugs, Doxycycline Monohydrate Capsules should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

DESCRIPTION

Doxycycline is a broad-spectrum antibiotic synthetically derived from oxytetracycline. Doxycycline Monohydrate Capsules 100 mg, 75 mg, and 50 mg contain Doxycycline Monohydrate equivalent to 100 mg, 75 mg, or 50 mg of doxycycline for oral administration. The chemical designation of the light-yellow crystalline powder is alpha-6-deoxy-5-oxytetracycline.

Structural formula:

C22H24N2O8 • H2O         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: colloidal silicon dioxide; magnesium stearate; microcrystalline cellulose; sodium starch glycolate; and a hard gelatin capsule which contains black iron oxide, red iron oxide, titanium dioxide, and yellow iron oxide for the 100 mg and 75 mg strengths, titanium dioxide and yellow iron oxide for the 50 mg strength. The capsules are printed with edible ink containing black iron oxide, red iron oxide, and yellow iron oxide for the 50 mg and 100 mg strengths and black iron oxide, FD&C Blue No. 2, FD&C Red No. 40, FD&C Blue No. 1, and D&C Yellow No. 10 for the 75 mg strength.

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.	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	2.60 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: 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 gram-negative 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	Haemophilus ducreyi
Brucella species	Haemophilus influenzae
Calymmatobacterium granulomatis	Neisseria gonorrhoeae
Campylobacter fetus	Vibrio cholerae
Francisella tularensis	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	Klebsiella species
Enterobacter aerogenes	Shigella species
Escherichia coli

Anaerobic Microorganisms:

Actinomyces israelii	Fusobacterium fusiforme
Clostridium species

Other Microorganisms:

Borrelia recurrentis	Rickettsiae
Chlamydia psittaci	Treponema pallidum
Chlamydia trachomatis	Treponema pertenue
Mycoplasma pneumoniae

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:

Interpretive criteria for Enterobacteriaceae, Staphylococcus aureus and Acinetobacter spp.
Microorganism	MIC Interpretive Standard (μg/mL)
	Susceptible (S)	Intermediate (I)	Resistant (R)
Enterobacteriaceae	≤ 4	8	≥ 16
Staphylococcus aureus
Acinetobacter spp.

Microorganisms that are susceptible to tetracycline are generally susceptible to doxycycline.

Interpretive Criteria for Haemophilus spp.
Microorganism	MIC Interpretive Standard (μg/mL)
	Susceptible (S)	Intermediate (I)	Resistant (R)
Haemophilus spp.	≤ 2	4	≥ 8

Interpretive criteria for Haemophilus spp. are applicable only to tests performed by broth microdilution method using Haemophilus Test Medium (HTM).1,3


Microorganisms that are susceptible to tetracycline are generally susceptible to doxycycline.

Interpretive Criteria for Neisseria gonorrhoeae
Microorganism	MIC Interpretive Standard (μg/mL)
	Susceptible (S)	Intermediate (I)	Resistant (R)
Neisseria gonorrhoeae	≤ 0.25	0.5 - 1	≥ 2

Interpretive criteria for Neisseria gonorrhoeae are applicable only to tests performed by agar dilution method using GC agar base with 1% defined growth supplement.1,3


Microorganisms that are susceptible to tetracycline are generally susceptible to doxycycline.

Interpretive Criteria for Streptococcus pneumoniae
Microorganism	MIC Interpretive Standard (μg/mL)
	Susceptible (S)	Intermediate (I)	Resistant (R)
Streptococcus pneumoniae	≤ 2	4	≥ 8

Interpretive criteria for Streptococcus pneumoniae are applicable only to tests performed by broth microdilution method using Cation-Adjusted Mueller-Hinton broth with 2.5% - 5% lysed horse blood.1,3


Microoganisms that are susceptible to tetracycline are generally susceptible to doxycycline.

Interpretive Criteria for Bacillus anthracis and Brucella spp.
Microorganism	MIC Interpretive Standard (μg/mL)
	Susceptible (S)	Intermediate (I)	Resistant (R)
Bacillus anthracis	≤ 1	-	-
Brucella spp.

Broth Microdilution performed in unsupplemented Brucella broth pH adjusted to 7.1 ± 0.1 for Brucella spp.5


For some organism/antimicrobial agent combinations, the absence or rare occurrence of resistant strains precludes defining results for categories other than “susceptible.”  For strains yielding results suggestive of a “nonsusceptible” category, organism identification and antimicrobial susceptibility test results should be confirmed.5

Incubation in 5% CO2 may be required for growth of some strains of Brucella spp. especially B. abortus. 

Incubation broth MIC tests in CO2 may decrease the MIC of tetracyclines, usually by one doubling dilution.5


Microorganisms that are susceptible to tetracycline are generally susceptible to doxycycline.

Interpretive Criteria for Burkholderia mallei, Burkholderia pseudomallei and Yersinia pestis
Microorganism	MIC Interpretive Standard (μg/mL)
	Susceptible (S)	Intermediate (I)	Resistant (R)
Burkholderia mallei	≤ 4	8	≥ 16
Burkholderia pseudomallei
Yersinia pestis

Microorganisms that are susceptible to tetracycline are generally susceptible to doxycycline.

Interpretive Criteria for Franciscella tularensis
Microorganism	MIC Interpretive Standard (μg/mL)
	Susceptible (S)	Intermediate (I)	Resistant (R)
Franciscella tularensis	≤ 4	-	-

Broth Microdilutions performed in Cation-Adjusted Mueller-Hinton broth with 2% defined growth supplement for Franciscella tularensis5

For some organism/antimicrobial agent combinations, the absence or rare occurrence of resistant strains precludes defining results for categories other than “susceptible.”  For strains yielding results suggestive of a “nonsusceptible” category, organism identification and antimicrobial susceptibility test results should be confirmed.5

Microorganisms that are susceptible to tetracycline are generally susceptible to doxycycline.

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:

Quality Control Ranges for MIC Broth Dilution Method

* Range applicable only to tests performed by broth microdilution method using Haemophilus Test Medium (HTM).1,3 † Range applicable only to tests performed by agar dilution method using GC agar base with 1% defined growth supplement.1,3 ‡ Range applicable only to tests performed by broth microdilution method using Cation-Adjusted Mueller-Hinton broth with 2.5% to 5% lysed horse blood.1,3
Microorganism	ATCC Number	Cation-Adjusted Mueller-Hinton (CAMHB) MIC (μg/mL)
Escherichia coli	25922	0.5 - 2
Haemophilus influenzae	49247	4 - 32*
Neisseria gonorrhoeae	49226	0.25 - 1†
Pseudomonas aeruginosa	27853	8 - 32
Staphylococcus aureus	29213	0.12 - 1
Streptococcus pneumoniae	49619	0.06 - 0.5‡

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 procedure2,3 requires the use of standardized inoculum concentrations. This procedure uses paper disks impregnated with 30-μg tetracycline or 30-μg doxycycline to test the susceptibility of microorganisms to doxycycline.

Reports from the laboratory providing results of the standard single-disk susceptibility test with a 30-μg tetracycline-class disk or the 30-μg doxycycline disk should be interpreted according to the following criteria:

Interpretive Zone Diameters for Staphylococcus aureus
Antimicrobial Agent	Zone Diameter (nearest whole mm)
	Susceptible (S)	Intermediate (I)	Resistant (R)
Tetracycline	≥ 19	15 - 18	≤ 14
Doxycycline	≥ 16	13 - 15	≤ 12

Interpretive Zone Diameters for Enterobacteriaceae.
Antimicrobial Agent	Zone Diameter (nearest whole mm)
	Susceptible (S)	Intermediate (I)	Resistant (R)
Tetracycline	≥ 15	12 - 14	≤ 11
Doxycycline	≥ 14	11 - 13	≤ 10
Minocycline	≥ 16	13 - 15	≤ 12

Interpretive Zone Diameters for Acinetobactor spp.
Antimicrobial Agent	Zone Diameter (nearest whole mm)
	Susceptible (S)	Intermediate (I)	Resistant (R)
Tetracycline	≥ 15	12 - 14	≤ 11
Doxycycline	≥ 13	10 - 12	≤ 9
Minocycline	≥ 16	13 - 15	≤ 12

 

Interpretive Zone Diameters for Haemophilus spp.
Antimicrobial Agent	Zone Diameter (nearest whole mm)
	Susceptible (S)	Intermediate (I)	Resistant (R)
Tetracycline	≥ 29	26 - 28	≤ 25

Interpretive criteria applicable only to tests performed by disk diffusion method using a 30-μg tetracycline-class disk and using Haemophilus Test Medium (HTM).2,3


Microorganisms that are susceptible to tetracycline are generally susceptible to doxycycline.

Interpretive Zone Diameters for Neisseria gonorrhoeae
Antimicrobial Agent	Zone Diameter (nearest whole mm)
	Susceptible (S)	Intermediate (I)	Resistant (R)
Tetracycline	≥ 38	31 - 37	≤ 30

Interpretive criteria applicable only to tests performed by disk diffusion method using a 30-μg tetracycline-class disk and using GC agar base with 1% defined growth supplement.2,3

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 μg/mL).


Microorganisms that are susceptible to tetracycline are generally susceptible to doxycycline.

Interpretive Zone Diameters for Streptococcus pneumoniae
Antimicrobial Agent	Zone Diameter (nearest whole mm)
	Susceptible (S)	Intermediate (I)	Resistant (R)
Tetracycline	≥ 23	19 - 22	≤ 18

Interpretative criteria applicable only to tests performed by disk diffusion method using a 30-μg tetracycline-class disk and using Mueller-Hinton agar with 5% defibrinated sheep blood and incubated in 5% CO2.2,3


Microorganisms that are susceptible to tetracycline are generally susceptible to doxycycline.

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-μg tetracycline-class disk or the 30-μg doxycycline disk should provide the following zone diameters in these laboratory test quality control strains:

Quality Control Zone Diameters for Disk Diffusion Method

* Range applicable only to tests performed by disk diffusion method using a 30-μg tetracycline-class disk and using Haemophilus Test Medium (HTM).2,3 † Range applicable only to tests performed by disk diffusion method using a 30-μg tetracycline-class disk and using GC agar base with 1% defined growth supplement.2,3 ‡ Range applicable only to tests performed by disk diffusion method using a 30-μg tetracycline-class disk and using Mueller-Hinton agar with 5% defibrinated sheep blood and incubated in 5% CO2. 2,3
Microorganism	ATCC Number	Zone Diameter (mm)
		Tetracycline		Doxycycline		Minocycline
Escherichia coli	25922	18 - 25		18 - 24		19 - 25
Haemophilus influenzae	49247	14 - 22*		-		-
Neisseria gonorrhoeae	49226	30 - 42†		-		-
Staphylococcus aureus	25923	24 - 30		23 - 29		25 - 30
Streptococcus pneumoniae	49619	27 - 31‡		-		-

Anaerobic Techniques:

For anaerobic bacteria, the susceptibility to tetracycline as MIC’s can be determined by standardized test methods.3,4 The MIC values obtained should be interpreted according to the following criteria:

Agar Dilution Interpretive Criteria for Anaerobes

Microorganism	MIC Interpretive Standard (μg/mL)
	Susceptible (S)	Intermediate (I)	Resistant (R)
Anaerobes	≤ 4	8	≥ 16

Microorganisms that are susceptible to tetracycline are generally susceptible to doxycycline.


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:

Quality Control Ranges for MIC Agar Dilution Method

Microorganism	ATCC Number	MIC (μg/mL)
Bacteroides fragilis	25285	0.125 - 0.5
Bacteroides thetaiotamicron	29741	8 - 32

Range applicable only to tests performed by the reference agar dilution method.

INDICATIONS AND USAGE

To reduce the development of drug-resistant bacteria and maintain effectiveness of Doxycycline Monohydrate Capsules and other antibacterial drugs, Doxycycline Monohydrate Capsules 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.

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 Chlamydia 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 (formerly Pasteurella pestis).

    Tularemia due to Francisella tularensis (formerly Pasteurella tularensis).

    Cholera caused by Vibrio cholerae (formerly Vibrio comma).

    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 microorganisms, when bacteriologic testing indicates appropriate susceptibility to the drug:

    Escherichia coli

    Enterobacter aerogenes (formerly Aerobacter aerogenes)

    Shigella species

    Acinetobacter species (formerly Mima species and Herellea 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). 

    Skin and skin structure infections caused by Staphylococcus aureus.

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

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

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.

CONTRAINDICATIONS

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

WARNINGS

THE USE OF DRUGS OF THE TETRACYCLINE CLASS DURING TOOTH DEVELOPMENT (LAST HALF OF PREGNANCY, INFANCY, AND CHILDHOOD TO THE AGE OF 8 YEARS) MAY CAUSE PERMANENT DISCOLORATION OF THE TEETH (YELLOW-GRAY-BROWN). This adverse reaction is more common during long-term use of the drugs but has been observed following repeated short-term courses. Enamel hypoplasia has also been reported. TETRACYCLINE DRUGS, THEREFORE, SHOULD NOT BE USED IN THIS AGE GROUP, EXCEPT FOR ANTHRAX, INCLUDING INHALATIONAL ANTHRAX (POST-EXPOSURE), UNLESS OTHER DRUGS ARE NOT LIKELY TO BE EFFECTIVE OR ARE CONTRAINDICATED.

Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Doxycycline Monohydrate Capsules, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

All tetracyclines form a stable calcium complex in any bone-forming tissue. A decrease in the fibula growth rate has been observed in prematures given oral tetracycline in doses of 25 mg/kg every six hours. This reaction was shown to be reversible when the drug was discontinued.

Results of animal studies indicate that tetracyclines cross the placenta, are found in fetal tissues, and can have toxic effects on the developing fetus (often related to retardation of skeletal development). Evidence of embryo toxicity has been noted in animals treated early in pregnancy. If any tetracycline is used during pregnancy or if the patient becomes pregnant while taking these drugs, the patient should be apprised of the potential hazard to the fetus.

The antianabolic action of the tetracyclines may cause an increase in BUN. Studies to date indicate that this does not occur with the use of doxycycline in patients with impaired renal function.

Photosensitivity manifested by an exaggerated sunburn reaction has been observed in some individuals taking tetracyclines. Patients apt to be exposed to direct sunlight or ultraviolet light should be advised that this reaction can occur with tetracycline drugs, and treatment should be discontinued at the first evidence of skin erythema.

PRECAUTIONS

General:

As with other antibiotic preparations, use of this drug may result in overgrowth of non-susceptible organisms, including fungi. If superinfection occurs, the antibiotic should be discontinued and appropriate therapy instituted.

Bulging fontanels in infants and benign intracranial hypertension in adults have been reported in individuals receiving tetracyclines. These conditions disappeared when the drug was discontinued.

Incision and drainage or other surgical procedures should be performed in conjunction with antibiotic therapy when indicated.

Prescribing Doxycycline Monohydrate Capsules in the absence of proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Information for Patients:

All patients taking doxycycline should be advised:

–to avoid excessive sunlight or artificial ultraviolet light while receiving doxycycline and to discontinue therapy if phototoxicity (e.g., skin eruptions, etc.) occurs. Sunscreen or sunblock should be considered. (See WARNINGS.)

–to drink fluids liberally along with doxycycline to reduce the risk of esophageal irritation and ulceration. (See ADVERSE REACTIONS.)

–that the absorption of tetracyclines is reduced when taken with foods, especially those which contain calcium. However, the absorption of doxycycline is not markedly influenced by simultaneous ingestion of food or milk. (See Drug Interactions.)

–that the absorption of tetracyclines is reduced when taking bismuth subsalicylate. (See Drug Interactions.)

–not to use outdated or poorly stored doxycycline.

–that the use of doxycycline might increase the incidence of vaginal candidiasis.

Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.

Patients should be counseled that antibacterial drugs including Doxycycline Monohydrate Capsules should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Doxycycline Monohydrate capsules are prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Doxycycline Monohydrate Capsules or other antibacterial drugs in the future.

Laboratory Tests:

In venereal disease when coexistent syphilis is suspected, a dark-field examination should be done before treatment is started and the blood serology repeated monthly for at least four months.

In long-term therapy, periodic laboratory evaluations of organ systems, including hematopoietic, renal, and hepatic studies should be performed.

Drug Interactions:

Because tetracyclines have been shown to depress plasma prothrombin activity, patients who are on anticoagulant therapy may require downward adjustment of their anticoagulant dosage.

Since bacteriostatic drugs may interfere with the bactericidal action of penicillin, it is advisable to avoid giving tetracyclines in conjunction with penicillin.

Absorption of tetracyclines is impaired by antacids containing aluminum, calcium, or magnesium, and iron-containing preparations.

Barbiturates, carbamazepine, and phenytoin decrease the half-life of doxycycline.

The concurrent use of tetracycline and methoxyflurane has been reported to result in fatal renal toxicity.

Concurrent use of tetracycline may render oral contraceptives less effective.

Drug/Laboratory Test Interactions:

False elevations of urinary catecholamine levels may occur due to interference with the fluorescence test.

Carcinogenesis, Mutagenesis, Impairment of Fertility:

Long-term studies in animals to evaluate the carcinogenic potential of doxycycline have not been conducted. However, there has been evidence of oncogenic activity in rats in studies with related antibiotics, oxytetracycline (adrenal and pituitary tumors) and minocycline (thyroid tumors). Likewise, although mutagenicity studies of doxycycline have not been conducted, positive results in in vitro mammalian cell assays have been reported for related antibiotics (tetracycline, oxytetracycline). Doxycycline administered orally at dosage levels as high as 250 mg/kg/day had no apparent effect on the fertility of female rats. Effect on male fertility has not been studied.

Pregnancy:

Teratogenic Effects.

Pregnancy Category D:

There are no adequate and well-controlled studies on the use of doxycycline in pregnant short-term, first trimester exposure. There are no human data available to assess the effects of long-term therapy of doxycycline in pregnant women such as that proposed for treatment of anthrax exposure. An expert review of published data on experiences with doxycycline use during pregnancy by TERIS - the Teratogen Information System - concluded that therapeutic doses during pregnancy are unlikely to pose a substantial teratogenic risk (the quantity and quality of data were assessed as limited to fair), but the data are insufficient to state that there is no risk.6

A case-control study (18,515 mothers of infants with congenital anomalies and 32,804 mothers of infants with no congenital anomalies) shows a weak but marginally statistically significant association with total malformations and use of doxycycline anytime during pregnancy. (Sixty-three [0.19%] of the controls and 56 [0.30%] of the cases were treated with doxycycline.) This association was not seen when the analysis was confined to maternal treatment during the period of organogenesis (i.e., in the second and third months of gestation) with the exception of a marginal relationship with neural tube defect based on only two exposed cases.7

A small prospective study of 81 pregnancies describes 43 pregnant women treated for 10 days with doxycycline during early first trimester. All mothers reported their exposed infants were normal at 1 year of age.8

Labor and Delivery:

The effect of tetracyclines on labor and delivery is unknown.

Nursing Mothers:

Tetracyclines are excreted in human milk, however, the extent of absorption of tetracyclines, including doxycycline, by the breastfed infant is not known. Short-term use by lactating women is not necessarily contraindicated; however, the effects of prolonged exposure to doxycycline in breast milk are unknown.9 Because of the potential for adverse reactions in nursing infants from doxycycline, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. (See WARNINGS.)

Pediatric Use:

See WARNINGS and DOSAGE AND ADMINISTRATION sections.

ADVERSE REACTIONS

Due to oral doxycycline’s virtually complete absorption, side effects to the lower bowel, particularly diarrhea, have been infrequent. The following adverse reactions have been observed in patients receiving tetracyclines.

Gastrointestinal: Anorexia, nausea, vomiting, diarrhea, glossitis, dysphagia, enterocolitis, and inflammatory lesions (with monilial overgrowth) in the anogenital region. Hepatotoxicity has been reported. These reactions have been caused by both the oral and parenteral administration of tetracyclines. Rare instances of esophagitis and esophageal ulcerations have been reported in patients receiving capsule and tablet forms of drugs in the tetracycline class. Most of these patients took medications immediately before going to bed. (See DOSAGE AND ADMINISTRATION.)

Skin: Maculopapular and erythematous rashes, Stevens-Johnson syndrome, toxic epidermal necrolysis, and erythema multiforme have been reported. Exfoliative dermatitis has been reported but is uncommon. Photosensitivity is discussed above. (See WARNINGS.)

Renal Toxicity: Rise in BUN has been reported and is apparently dose related. (See WARNINGS.)

Hypersensitivity Rea

Isotretinoina Germed

Isotretinoina Germed may be available in the countries listed below.

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Isotretinoin

Isotretinoin is reported as an ingredient of Isotretinoina Germed in the following countries:

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