Doxycycline Hyclate

DOXYCYCLINE HYCLATE- doxycycline hyclate capsule
Major Pharmaceuticals

DOXYCYCLINE HYCLATE CAPSULES, USP
Rev. 12/18Rx Only

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

DESCRIPTION

Doxycycline Hyclate Capsules, USP, are an antibacterial drug synthetically derived from oxytetracycline. The structural formula of doxycycline monohydrate is:

with a molecular formula of C22H24N2O8•H2O and a molecular weight of 462.46. The chemical designation for doxycycline is 4‑ (Dimethylamino)‑1,4,4a,5,5a,6,11,12a‑octahydro‑3,5,10,12,12a‑pentahydroxy‑6‑methyl‑1,11‑dioxo‑2‑naphthacenecarboxamide monohydrate. The molecular formula for doxycycline hydrochloride hemiethanolate hemihydrate is (C22H24N2O8•HCl)2•C2H6O•H2O and the molecular weight is 1025.89. Doxycycline is a light yellow crystalline powder. Doxycycline hyclate is soluble in water, while doxycycline monohydrate is very slightly soluble in water.

Doxycycline has a high degree of lipoid solubility and a low affinity for calcium binding. It is highly stable in normal human serum. Doxycycline will not degrade into an epianhydro form.

Each capsule for oral administration contains doxycycline hyclate equivalent to 100 mg of doxycycline (anhydrous). Inactive ingredients: lactose monohydrate, microcrystalline cellulose, magnesium stearate.

The 100 mg capsule shell contains: gelatin, diacetylated monoglycerides, sucrose fatty acid esters, glacial acetic acid, sodium lauryl sulfate, colloidal silicon dioxide, FD&C Blue #1 and titanium dioxide. The printing ink may contain: Shellac Glaze, Iron Oxide Black, N‑Butyl Alcohol, Propylene Glycol, SDA 3A Alcohol, FD&C Blue #2, FD&C Red #40, FD&C Blue #1, D&C Yellow #10.

CLINICAL PHARMACOLOGY

Tetracyclines are readily absorbed and are bound to plasma proteins in varying degree. They are concentrated by the liver in the bile, and excreted in the urine and feces at high concentrations and in a biologically active form. Doxycycline is virtually completely absorbed after oral administration.

Following a 200 mg dose, normal adult volunteers averaged peak serum levels of 2.6 mcg/mL of doxycycline at 2 hours, decreasing to 1.45 mcg/mL at 24 hours. Excretion of doxycycline by the kidney is about 40% per 72 hours in individuals with normal function (creatinine clearance about 75 mL/min). This percentage excretion may fall as low as 1 to 5% per 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.

Results of animal studies indicate that tetracyclines cross the placenta and are found in fetal tissues.

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.

Resistance

Cross resistance with other tetracyclines is common.

Antimicrobial Activity

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 hyclate capsules.

Gram-Negative Bacteria
Acinetobacter species
Bartonella bacilliformis
Brucella species
Klebsiella species
Klebsiella granulomatis
Campylobacter fetus
Enterobacter aerogenes
Escherichia coli
Francisella tularensis
Haemophilus ducreyi
Haemophilus influenza
Neisseria gonorrhoeae
Shigella species
Vibrio cholerae
Yersinia pestis

Gram-Positive Bacteria
Bacillus anthracis
Listeria monocytogenes
Streptococcus pneumoniae

Anaerobic Bacteria
Clostridium species
Fusobacterium fusiforme
Propionibacterium acnes

Other Bacteria
Nocardiae and other aerobic Actinomyces species
Borrelia recurrentis
Chlamydophila psittaci
Chlamydia trachomatis
Mycoplasma pneumoniae
Rickettsiae
Treponema pallidum
Treponema pallidum subspecies pertenue
Ureaplasma urealyticum

Parasites
Balantidium coli
Entamoeba species
Plasmodium falciparum*

*Doxycycline has been found to be active against the asexual erythrocytic forms of Plasmodium falciparum , but not against the gametocytes of P. falciparum. The precise mechanism of action of the drug is not known.

Susceptibility Testing

For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.fda.gov/STIC.

INDICATIONS AND USAGE

To reduce the development of drug-resistant bacteria and maintain effectiveness of Doxycycline Hyclate Capsules, USP and other antibacterial drugs, Doxycycline Hyclate Capsules, USP should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Treatment

Doxycycline is indicated for the treatment of the following infections:

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Rocky Mountain spotted fever, typhus fever and the typhus group, Q fever, rickettsialpox, and tick fevers caused by Rickettsiae.

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Respiratory tract infections caused by Mycoplasma pneumoniae.

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Lymphogranuloma venereum caused by Chlamydia trachomatis.

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Psittacosis (ornithosis) caused by Chlamydophila psittaci.

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Trachoma caused by Chlamydia trachomatis , although the infectious agent is not always eliminated, as judged by immunofluorescence.

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Inclusion conjunctivitis caused by Chlamydia trachomatis.

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Uncomplicated urethral, endocervical, or rectal infections in adults caused by Chlamydia trachomatis.

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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:

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Chancroid caused by Haemophilus ducreyi.

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Plague due to Yersinia pestis.

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Tularemia due to Francisella tularensis.

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Cholera caused by Vibrio cholerae.

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Campylobacter fetus infections caused by Campylobacter fetus.

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Brucellosis due to Brucella species (in conjunction with streptomycin).

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Bartonellosis due to Bartonella bacilliformis.

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

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Escherichia coli.

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Enterobacter aerogenes.

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Shigella species.

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Acinetobacter species.

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Respiratory tract infections caused by Haemophilus influenzae.

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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:

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Upper respiratory infections caused by Streptococcus pneumoniae.

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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:

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Uncomplicated gonorrhea caused by Neisseria gonorrhoeae.

•

Syphilis caused by Treponema pallidum.

•

Yaws caused by Treponema pallidum subspecies pertenue.

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Listeriosis due to Listeria monocytogenes.

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Vincent’s infection caused by Fusobacterium fusiforme.

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Actinomycosis caused by Actinomyces israelii.

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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.