DOXYCYCLINE capsule

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Active ingredient:
DOXYCYCLINE (UNII: N12000U13O) (DOXYCYCLINE ANHYDROUS - UNII:334895S862)
Available from:
PharmPak, Inc.
Administration route:
ORAL
Prescription type:
PRESCRIPTION DRUG
Therapeutic indications:
To reduce the development of drug-resistant bacteria and maintain effectiveness of doxycycline capsules, USP and other antibacterial drugs, doxycycline 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. 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
Product summary:
Doxycycline Capsules, USP 100 mg have a brown opaque cap and a yellow opaque body. The capsules are imprinted “G&W 0555” with white ink on the cap and “100 mg” with brown ink on the body, filled with yellow to beige powder. Each capsule contains doxycycline monohydrate equivalent to 100 mg doxycycline. Doxycycline Capsules, USP 100 mg is available in: Bottles of 1 capsules ....................................................... NDC 54348-573-00  Bottles of 2 capsules ........................................................NDC 54348-573-02 Bottles of 14 capsules .......................................................NDC 54348-573-14 Bottles of 28 capsules .......................................................NDC 54348-573-28 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. PROTECT FROM LIGHT.
Authorization status:
Abbreviated New Drug Application
Authorization number:
54348-573-00, 54348-573-02, 54348-573-14, 54348-573-28

DOXYCYCLINE- doxycycline capsule

PharmPak, Inc.

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Doxycycline Capsules, USP

Rx only

To reduce the development of drug-resistant bacteria and maintain the effectiveness of

doxycycline capsules and other antibacterial drugs, doxycycline 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 antibacterial synthetically derived from oxytetracycline. Doxycycline

capsules USP, 75 mg, and 100 mg contain doxycycline monohydrate equivalent to 75 mg, and 100 mg of

doxycycline for oral administration. The chemical designation of the light yellow to pale yellow

powder is 2-Naphthacenecarboxamide, 4-(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-

3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-,[4 S-(4a,4a ,5 ,5a ,6 ,12a ,)]-, monohydrate.

Structural formula:

H

O 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 iron oxide black, iron oxide red, iron oxide

yellow, titanium dioxide, gelatin, sodium lauryl sulfate for the 75 mg strength and iron oxide black, iron

oxide red, iron oxide yellow, titanium dioxide, FD & C Red # 3, D&C Yellow # 10, gelatin, sodium

lauryl sulfate for the 100 mg strength. The capsules are printed with edible ink containing shellac,

titanium dioxide, black iron oxide, brown iron oxide and potassium hydroxide for 75 mg and 100 mg

strengths.

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):

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 1-5%/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:

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.

Res is tance

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 ( see INDICATIONS AND USAGE).

Gram-Negative Bacteria

Acinetobacter species

Bartonella bacilliformis

Brucella species

Campylobacter fetus

Enterobacter aerogenes

Escherichia coli

Francisella tularensis

Haemophilus ducreyi

Haemophilus influenzae

Klebsiella granulomatis

Klebsiella species

Neisseria gonorrhoeae

Shigella species

Vibrio cholera

Yersinia pestis

Gram-Positive Bacteria

Bacillus anthracis

Listeria monocytogenes

Streptococcus pneumoniae

Anaerobic Bacteria

Clostridium species

Fusobacterium fusiforme

Propionibacterium acnes

Other Bacteria

Nocardiae and other Actinomyces species

Borrelia recurrentis

Chlamydophila psittaci

Chlamydia trachomatis

Mycoplasma pneumoniae

Rickettsiae

Treponema pallidum

Treponema pallidum subspecies pertenue

Ureaplasma urealyticum

Parasites

Balantidium coli

Entamoeba species

Susceptibility Testing Methods

When available, the clinical microbiology laboratory should provide cumulative reports of in vitro

susceptibility test results for antimicrobial drugs used in local hospitals and practice areas as periodic

reports that describe the susceptibility profile of nosocomial and community-acquired pathogens.

These reports should aid the physician in selecting the most effective antimicrobial.

Dilution Techniques

Quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (MICs).

These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs

should be determined using a standardized test method (broth and /or agar).

The MIC values

should be interpreted according to criteria provided in Table 1.

Diffusion Techniques

Quantitative methods that require measurement of zone diameters can also provide reproducible

estimates of the susceptibility of bacteria to antimicrobial compounds. The zone size should be

determined using a standardized test method.

This procedure uses paper disks impregnated with 30

mcg doxycycline to test the susceptibility of microorganisms to doxycycline. The disk diffusion

interpretive criteria are provided in Table 1.

Anaerobic Techniques

For anaerobic bacteria, the susceptibility to doxycycline can be determined by a standardized test

method.

The MIC values obtained should be interpreted according to the criteria provided in Table

1,2,4,6,7

1,3,4

Table 1: Susceptibility Test Interpretive Criteria for Doxycycline and Tetracycline

* Organisms susceptible to tetracycline are also considered susceptible to doxycycline. However,

some organisms that are intermediate or resistant to tetracycline may be susceptible to doxycycline.

Bacteria*

Minimal Inhibitory

Concentration

(mcg per mL)

Zone Diameter

(mm)

Agar Dilution

(mcg per mL)

S

I

R

S

I

R

S

I

R

Acinetobacter spp.

Doxycycline

Tetracycline

≤ 4

≤ 4

≥ 16

≥ 16

≥ 13

≥ 13

10 to 12

10 to 12

≤ 9

≤ 11

Anaerobes

Tetracycline

≤ 4

≥ 16

Bacillus anthracis

Doxycycline

Tetracycline

≤ 1

≤ 1

Brucella species

Doxycycline

Tetracycline

≤ 1

≤ 1

Enterobacteriaceae

Doxycycline

Tetracycline

≤ 4

≤ 4

≥ 16

≥ 16

≥ 14

≥ 15

11 to 13

12 to 14

≤ 10

≤ 11

Franciscella tularensis

Doxycycline

Tetracycline

≤ 4

≤ 4

Haemophilus influenzae

Tetracycline

≤ 2

≥ 8

≥ 29

26 to 28

≤ 25

Mycoplasma pneumoniae

Tetracycline

≤ 2

Neisseria gonorrhoeae

Tetracycline

≥ 38

31 to 37

≤ 30

≤ 0.25

0.5 to 1

≥ 2

Nocardiae and other aerobic

Actinomyces species

Doxycycline

≤ 1

2 to4

≥ 8

Streptococcus pneumoniae

Doxycycline

Tetracycline

≤ 0.25

≤ 1

≥ 1

≥ 4

≥ 28

≥ 28

25 to 27

25 to 27

≤ 24

≤ 24

Vibrio cholerae

Doxycycline

Tetracycline

≤ 4

≤ 4

≥ 16

≥ 16

Yersinia pestis

Doxycycline

Tetracycline

≤ 4

≤ 4

≥ 16

≥ 16

Ureaplasma urealyticum

Tetracycline

≤ 1

≥ 2

The current absence of resistance isolates precludes defining any results other than “Susceptible”.

If isolates yielding MIC results other than susceptible, they should be submitted to a reference

laboratory

for further testing.

Gonococci with 30 mcg tetracycline disk zone diameters of less than 19 mm usually indicate a

plasmid-mediated tetracycline resistant Neisseria gonorrhoeae isolate. Resistance in these strains

should be confirmed by a dilution test (MIC ≥ 16 mcg per mL)

A report of Susceptible (S) indicates that the antimicrobial is likely to inhibit growth of the

microorganism if the antimicrobial drug reaches the concentration usually achievable at the site of

infection. A report of Intermediate (I) 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 product is

physiologically concentrated or in situations where high dosage of drug can be used. This category

also provides a buffer zone that prevents small uncontrolled technical factors from causing major

discrepancies in interpretation. A report of Resistant (R) indicates that the antimicrobial drug is not likely

to inhibit growth of the microorganism if the antimicrobial drug reaches the concentrations usually

achievable at the infection site; other therapy should be selected.

Quality Control

Standardized susceptibility test procedures require the use of laboratory controls to monitor and ensure

the accuracy and precision of the supplies and reagents used in the assay, and the techniques of the

individuals performing the test.

Standard doxycycline and tetracycline powders should

provide the following range of MIC values noted in Table 2. For the diffusion technique using the 30

mcg doxycycline disk or 30 mcg tetracycline disk, the criteria noted in Table 2 should be achieved.

Table 2: Acceptable Quality Control Ranges for Susceptibility Testing for Doxycycline and

Tetracycline

QC Strain

Minimal Inhibitory

Concentration

(mcg per mL)

Zone

Diameter

(mm)

Agar Dilution

(mcg per mL)

Enterococcus faecalis ATCC 29212

Doxycycline

Tetracycline

2 to 8

8 to 32

Escherichia coli ATCC 25922

Doxycycline

Tetracycline

0.5 to 2

0.5 to 2

18 to 24

18 to 25

Eggerthella lenta ATCC 43055

Doxycycline

2 to 16

Haemophilus influenzae ATCC 49247

Tetracycline

4 to 32

14 to 22

Neisseria gonorrhoeae ATCC 49226

Tetracycline

30 to 42

0.25 to 1

Staphylococcus aureus ATCC 25923

Doxycycline

Tetracycline

23 to 29

24 to 30

Staphylococcus aureus ATCC 29213

Doxycycline

0.12 to 0.5

1,2,3,4,5,6,7

* ATCC is the American Type Culture Collection

Tetracycline

0.12 to 1

Streptococcus pneumoniae ATCC 49619

Doxycycline

Tetracycline

0.015 to 0.12

0.06 to 0.5

25 to 34

27 to 31

Bacteroides fragilis ATCC 25285

Tetracycline

0.125 to 0.5

Bacteroides thetaiotaomicron ATCC 29741

Doxycycline

Tetracycline

2 to 8

8 to 32

Mycoplasma pneumoniae ATCC 29342

Tetracycline

0.06 to 0.5

0.06 to 0.5

Ureaplasma urealyticum ATCC 33175

Tetracycline

≥ 8

INDICATIONS AND USAGE

To reduce the development of drug-resistant bacteria and maintain effectiveness of doxycycline

capsules, USP and other antibacterial drugs, doxycycline 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.

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 C hlamydia 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

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

WARNINGS

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 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.

Intracranial hypertension (IH, pseudotumor cerebri) has been associated with the use of tetracyclines

including doxycycline capsules. 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 capsules 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.

PRECAUTIONS

General:

As with other antibacterial preparations, use of this drug may result in overgrowth of non-susceptible

organisms, including fungi. If superinfection occurs, doxycycline capsules should be discontinued and

appropriate therapy instituted.

Incision and drainage or other surgical procedures should be performed in conjunction with

antibacterial therapy when indicated.

Prescribing doxycycline 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 capsules should only be

used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When

doxycycline 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 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

antibacterial, 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 antibacterial (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.

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.

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.

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.

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:

Because of the effects of drugs of the tetracycline–class, on tooth development and growth, use

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. (see WARNINGS and DOSAGE AND

ADMINISTRATION).

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, and pancreatitis.

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 Reactions: Urticaria, angioneurotic edema, anaphylaxis, anaphylactoid purpura,

serum sickness, pericarditis, and exacerbation of systemic lupus erythematosus.

Blood: Hemolytic anemia, thrombocytopenia, neutropenia, and eosinophilia have been reported with

tetracyclines.

Other: Intracranial hypertension (IH, pseudotumor cerebri) has been associated with the use of

tetracyclines. (See PRECAUTIONS- General.)

When given over prolonged periods, tetracyclines have been reported to produce brown-black

microscopic discoloration of the thyroid gland. No abnormalities of thyroid function are known to

occur.

To report SUSPECTED ADVERSE REACTIONS, contact G&W Laboratories, Inc. at 1-800-

922-1038 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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.

DOSAGE AND ADMINISTRATION

THE USUAL DOSAGE AND FREQUENCY OF ADMINISTRATION OF DOXYCYCLINE

DIFFERS FROM THAT OF THE OTHER TETRACYCLINES. EXCEEDING THE

RECOMMENDED DOSAGE MAY RESULT IN AN INCREASED INCIDENCE OF SIDE EFFECTS.

Adults: The usual dose of oral doxycycline is 200 mg on the first day of treatment (administered 100

mg every 12 hours or 50 mg every 6 hours) followed by a maintenance dose of 100 mg/day. The

maintenance dose may be administered as a single dose or as 50 mg every 12 hours. In the management

of more severe infections (particularly chronic infections of the urinary tract), 100 mg every 12 hours

is recommended.

Pediatric Patients:

For all pediatric patients weighing less than 45 kg with severe or life-threatening infections (e.g.

anthrax, Rocky Mountain spotted fever), the recommended dosage is 2.2 mg/kg of body weight

administered every 12 hours. Children weighing 45 kg or more should receive the adult dose (see

WARNINGSand PRECAUTIONS).

For pediatric patients with less severe disease (greater than 8 years of age and weighing less than 45

kg), the recommended dosage schedule is 4.4 mg per kg of body weight divided into two doses on the

first day of treatment, followed by a maintenance dose of 2.2 mg per kg of body weight (given as a

single daily dose or divided into twice daily doses). For pediatric patients weighing over 45 kg, the

usual adult dose should be used.

The therapeutic antibacterial serum activity will usually persist for 24 hours following recommended

dosage.

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

Administration of adequate amounts of fluid along with capsule and tablet forms of drugs in the

tetracycline class is recommended to wash down the drugs and reduce the risk of esophageal irritation

and ulceration. (See ADVERSE REACTIONS)

If gastric irritation occurs, it is recommended that doxycycline be given with food or milk. The

absorption of doxycycline is not markedly influenced by simultaneous ingestion of food or milk.

Studies to date have indicated that administration of doxycycline at the usual recommended doses does

not lead to excessive accumulation of doxycycline in patients with renal impairment.

Uncomplicated gonococcal infections in adults (except anorectal infections in men): 100 mg, by

mouth, twice a day for 7 days. As an alternate single visit dose, administer 300 mg stat followed in one

hour by a second 300 mg dose.

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

days.

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

Uncomplicated urethral, endocervical, or rectal infection in adults caused by

Chlamydia trachomatis: 100 mg, by mouth, twice a day for at least 7 days.

Nongonococcal urethritis caused by C. trachomatis and U. urealyticum: 100 mg, by mouth, twice a

day for at least 7 days.

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

days.

Inhalational anthrax (post-exposure): ADULTS: 100 mg of doxycycline, by mouth, twice a day for

60 days. CHILDREN: weighing less than 45 kg 2.2 mg/kg of body weight, by mouth, twice a day for 60

days. Children weighing 45 kg or more should receive the adult dose.

HOW SUPPLIED

Doxycycline Capsules, USP 100 mg have a brown opaque cap and a yellow opaque body. The capsules

are imprinted “G&W 0555” with white ink on the cap and “100 mg” with brown ink on the body, filled

with yellow to beige powder. Each capsule contains doxycycline monohydrate equivalent to 100 mg

doxycycline.

Doxycycline Capsules, USP 100 mg is available in:

Bottles of 1 capsules ....................................................... NDC 54348-573-00

Bottles of 2 capsules ........................................................NDC 54348-573-02

Bottles of 14 capsules .......................................................NDC 54348-573-14

Bottles of 28 capsules .......................................................NDC 54348-573-28

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.

PROTECT FROM LIGHT.

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 PO

, and methacycline; in

minipigs by doxycycline, minocycline, tetracycline PO

, and methacycline; in dogs by doxycycline and

minocycline; in monkeys by minocycline.

Minocycline, tetracycline PO

, 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. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial

Susceptibility Testing; Twenty-seventh Informational Supplement, CLSI document M100-S27

[2017]. CLSI document M100S23, Clinical and Laboratory Standards Institute, 950 West Valley

Road, Suite 2500, Wayne, Pennsylvania 19087, USA.

2. Clinical and Laboratory Standards Institute (CLSI). 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.

3. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Disk

Diffusion 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.

4. Clinical and Laboratory Standards Institute (CLSI). 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.

5. 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.

6. Clinical and Laboratory Standards Institute (CLSI). Methods for 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.

7. Clinical and Laboratory Standards Institute (CLSI). 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.

8. Friedman JM and Polifka JE. Teratogenic Effects of Drugs. A Resource for Clinicians (TERIS).

Baltimore, MD: The Johns Hopkins University Press: 2000: 149-195.

9. Cziezel AE and Rockenbauer M. Teratogenic study of doxycycline. Obstet Gynecol 1997; 89:524-

528.

10. Horne HW Jr. and Kundsin RB. The role of mycoplasma among 81 consecutive pregnancies: a

prospective study. Int J Fertil 1980; 25:315-317.

11. Hale T. Medications and Mothers Milk. 9

edition. Amarillo, TX: Pharmasoft Publishing 2000; 225-

226.

Rx only

Manufactured by:

G&W Laboratories, Inc.

South Plainfield, NJ 07080

8-DOXYGWSV2

Rev. 04/2017

Package Labeling: 54348-573-00

Package Labeling: 54348-573-02

Package Labeling: 54348-573-14

Package Labeling: 54348-573-28

DOXYCYCLINE

doxycycline capsule

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:54348 -573(NDC:0 713-0 555)

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

DO XYCYCLINE (UNII: N120 0 0 U13O) (DOXYCYCLINE ANHYDROUS - UNII:3348 9 5S8 6 2)

DOXYCYCLINE ANHYDROUS 10 0 mg

Inactive Ingredients

Ingredient Name

Stre ng th

FERRO SO FERRIC O XIDE (UNII: XM0 M8 7F357)

FERRIC O XIDE RED (UNII: 1K0 9 F3G6 75)

FERRIC O XIDE YELLO W (UNII: EX438 O2MRT)

TITANIUM DIO XIDE (UNII: 15FIX9 V2JP)

GELATIN (UNII: 2G8 6 QN327L)

SO DIUM LAURYL SULFATE (UNII: 36 8 GB5141J)

SHELLAC (UNII: 46 N10 7B71O)

PO TASSIUM HYDRO XIDE (UNII: WZH3C48 M4T)

SILICO N DIO XIDE (UNII: ETJ7Z6 XBU4)

MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )

CELLULO SE, MICRO CRYSTALLINE (UNII: OP1R32D6 1U)

SO DIUM STARCH GLYCO LATE TYPE A PO TATO (UNII: 58 56 J3G2A2)

BRO WN IRO N O XIDE (UNII: 1N0 32N7MFO)

PharmPak, Inc.

Product Characteristics

Color

yello w (Opaque Bo dy) , bro wn (Opaque Cap)

S core

no sco re

S hap e

CAPSULE

S iz e

19 mm

Flavor

Imprint Code

GW;0 555;10 0 ;mg

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:54348 -573-0 0

1 in 1 BOX

0 7/12/20 19

1

1 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

2

NDC:54348 -573-0 2

1 in 1 BOX

0 7/12/20 19

2

2 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

3

NDC:54348 -573-14

1 in 1 BOX

0 7/12/20 19

3

14 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

4

NDC:54348 -573-28

1 in 1 BOX

0 7/12/20 19

4

28 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA20 4446

0 7/12/20 19

Labeler -

PharmPak, Inc. (175493840)

Revised: 8/2019

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