DESCRIPTION
id: 9544192d-aa08-4a08-ac5b-b39ece8068e2
displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3
Doxycycline is a broad-spectrum antibacterial synthetically derived from oxytetracycline. Doxycycline Capsules USP, 100 mg, 75 mg, and 50 mg capsules 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:
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 and sodium starch glycolate Type A Potato. Hard gelatin capsule contains black iron oxide, gelatin, red iron oxide, titanium dioxide and yellow iron oxide. The capsules are printed with edible ink containing black iron oxide, potassium hydroxide, propylene glycol, shellac and titanium dioxide.
CLINICAL PHARMACOLOGY
id: da5e195e-9e3b-4ec0-954a-ad10600fb59f
displayName: CLINICAL PHARMACOLOGY SECTION
FDA Article Code: 34090-1
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 (mcg/mL)
|
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.
INDICATIONS AND USAGE
id: f19d11ea-9994-4c5a-a8cb-60ec6e773b4c
displayName: INDICATIONS & USAGE SECTION
FDA Article Code: 34067-9
To reduce the development of drug-resistant bacteria and maintain effectiveness of doxycycline and other antibacterial drugs,
Doxycycline 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 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.
Brucellosis due to Brucella species (in conjunction with streptomycin).
Bartonellosis due to Bartonella bacilliformis.
Granuloma inguinale caused by Klebsiella 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
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.
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 pallidum subspecies 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
id: 753f41c0-6e39-4e87-b4d2-fc71df2ca929
displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3
This drug is contraindicated in persons who have shown hypersensitivity to any of the tetracyclines.
WARNINGS
id: 1ef3e38a-c472-4e18-ad85-b2224fe5ad2c
displayName: WARNINGS SECTION
FDA Article Code: 34071-1
The use of drugs of the tetracycline class, including doxycycline, 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 it has been observed following repeated short-term courses. Enamel hypoplasia has also been reported. Use of doxycycline in pediatric patients 8 years of age or less only when the potential benefits are expected to outweigh the risks in severe or life-threatening conditions (e.g. anthrax, Rocky Mountain spotted fever), particularly when there are no alternative therapies.
Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including doxycycline, 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.
Intracranial hypertension (IH, pseudotumor cerebri) has been associated with the use of tetracyclines including doxycycline. Clinical manifestations of IH include headache, blurred vision, diplopia, and vision loss; papilledema can be found on fundoscopy. Women of childbearing age who are overweight or have a history of IH are at greater risk for developing tetracycline associated IH. Concomitant use of isotretinoin and doxycycline should be avoided because isotretinoin is also known to cause pseudotumor cerebri.
Although IH typically resolves after discontinuation of treatment, the possibility for permanent visual loss exists. If visual disturbance occurs during treatment, prompt ophthalmologic evaluation is warranted. Since intracranial pressure can remain elevated for weeks after drug cessation patients should be monitored until they stabilize.
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.
ADVERSE REACTIONS
id: 73c187a9-66ea-4b25-b23e-027e94044c03
displayName: ADVERSE REACTIONS SECTION
FDA Article Code: 34084-4
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.
OVERDOSAGE
id: 4003fc78-8109-4d36-9f0d-b7d9f38b6f11
displayName: OVERDOSAGE SECTION
FDA Article Code: 34088-5
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.
DOSAGE AND ADMINISTRATION
id: 93625e37-b817-4c97-b5f7-f296a5f24c74
displayName: DOSAGE & ADMINISTRATION SECTION
FDA Article Code: 34068-7
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.
HOW SUPPLIED
id: 8f5f0110-a793-4140-96c0-f5270e3ef067
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5
Doxycycline capsules USP, 50 mg are brown opaque cap and yellow opaque body imprinted with “LU” on cap in white ink and “M71” on the body in black ink filled with light yellow to grey colored blend.
Each capsule contains doxycycline monohydrate USP equivalent to 50 mg doxycycline.
Doxycycline capsules USP, 50 mg is available in:
Bottle of 100 capsules NDC 68180-650-01
Doxycycline capsules USP, 75 mg are brown opaque cap and light yellow opaque body imprinted with “LU” on cap in white ink and “M72” on the body in black ink filled with light yellow to grey colored blend.
Each capsule contains doxycycline monohydrate USP equivalent to 75 mg doxycycline.
Doxycycline capsules USP, 75 mg is available in:
Bottle of 100 capsules NDC 68180-651-01
Doxycycline capsules USP, 100 mg are brown opaque cap and yellow opaque body imprinted with “LU” on cap in white ink and “M73” on the body in black ink filled with light yellow to grey colored blend.
Each capsule contains doxycycline monohydrate USP equivalent to 100 mg doxycycline.
Doxycycline capsules USP, 100 mg is available in:
Bottle of 50 capsules NDC 68180-652-08
Bottle of 250 capsules NDC 68180-652-29
Store at 25°C (77°F); excursions permitted to 15 to 30°C (59 to 86°F) [see USP controlled room temperature]. Protect from light.
Dispense in a tight, light-resistant container as defined in the USP/NF.
ANIMAL PHARMACOLOGY AND ANIMAL TOXICOLOGY
id: ce8b4007-4086-4f06-b783-d3f66b04555b
displayName: ANIMAL PHARMACOLOGY & OR TOXICOLOGY SECTION
FDA Article Code: 34091-9
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
id: f04e5eda-5e09-43c3-b276-e8a3dfac9844
displayName: REFERENCES SECTION
FDA Article Code: 34093-5
- Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing; Twenty-seventh Informational Supplement, CLSI document M100-S27 [2017]. Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA.
- Clinical and Laboratory Standards Institute. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard – Tenth Edition. CLSI document M07- A10 [2015], Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA.
- Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Disk Susceptibility Tests; Approved Standard – Twelfth Edition. CLSI document M02-A12 [2015], Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA.
- Clinical and Laboratory Standards Institute. Methods for Antimicrobial Dilution and Disk Susceptibility Testing of Infrequently Isolated or Fastidious Bacteria; Approved Guideline – Third Edition. CLSI document M45-A3 [2015], Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA.
- Clinical and Laboratory Standards Institute (CLSI). Methods for Antimicrobial Susceptibility Testing of Anaerobic Bacteria; Approved Standard – Eighth Edition. CLSI document M11-A8 [2012], Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, PA 19087 USA.
- Clinical and Laboratory Standards Institute. Susceptibility Testing of Mycobacteria, Nocardiae, and Other Aerobic Actinomycetes; Approved Standard – Second Edition. CLSI document M24-A2 [2011], Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA.
- Clinical and Laboratory Standards Institute. Methods for Antimicrobial Susceptibility Testing for Human Mycoplasmas; Approved Guideline. CLSI document M43-A [2011], Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA.
- Friedman JM and Polifka JE. Teratogenic Effects of Drugs. A Resource for Clinicians (TERIS). Baltimore, MD: The Johns Hopkins University Press: 2000: 149-195.
- 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.
- Hale T. Medications and Mothers Milk. 9th edition. Amarillo, TX: Pharmasoft Publishing 2000; 225-226.
Manufactured for:
Lupin Pharmaceuticals, Inc.
Baltimore, Maryland 21202
United States.
Manufactured by:
Lupin Limited
Goa 403 722
INDIA.
Revised: July 2017 ID#: 251702
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
id: a671842c-20f1-4539-9d45-7718b706db2e
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4
Doxycycline Capsules USP, 50 mg
Rx only
NDC 68180-650-01: Bottle of 100 capsules
Doxycycline Capsules USP, 75 mg
Rx only
NDC 68180-651-01: Bottle of 100 capsules
Doxycycline Capsules USP, 100 mg
Rx only
NDC 68180-652-08: Bottle of 50 capsules
