DOXYCYCLINE- doxycycline tablet, film coated
Lannett Company, Inc.

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Doxycycline Tablets, USP

Rx Only

To reduce the development of drug-resistant bacteria and maintain the effectiveness of doxycycline tablets and other antibacterial drugs, doxycycline tablets 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 Tablets USP, 150 mg, 100 mg, 75 mg and 50 mg, contain doxycycline monohydrate equivalent to 150 mg, 100 mg, 75 mg, and 50 mg of doxycycline for oral administration. Inactive ingredients include microcrystalline cellulose, anhydrous lactose, corn starch, magnesium stearate, colloidal silicon dioxide, polyvinyl alcohol, polyethylene glycol, talc, titanium dioxide, D&C yellow #10 aluminum lake, and FD&C yellow #6 aluminum lake. The chemical designation of the light-yellow crystalline powder 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.

Structural formula:

Chemical Structure

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.

CLINICAL PHARMACOLOGY

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

Following a 200 mg dose of doxycycline monohydrate, 24 normal adult volunteers averaged the following serum concentration values:

Time (hr): 0.5 1.0 1.5 2.0 3.0 4.0 8.0 12.0 24.0 48.0 72.0
Conc. (mcg/mL): 1.02 2.26 2.67 3.01 3.16 3.03 2.03 1.62 0.95 0.37 0.15
Average Observed Values
Maximum Concentration 3.61 mcg/mL (± 0.9 sd)
Time of Maximum Concentration 2.60 hr (± 1.10 sd)
Elimination Rate Constant 0.049 per hr (± 0.030 sd)
Half-Life 16.33 hr (± 4.53 sd)

Excretion of doxycycline by the kidney is about 40%/72 hours in individuals with normal function (creatinine clearance about 75 mL/min). This percentage excretion may fall as low as 1 to 5%/72 hours in individuals with severe renal insufficiency (creatinine clearance below 10 mL/min). Studies have shown no significant difference in serum half-life of doxycycline (range 18 to 22 hours) in individuals with normal and severely impaired renal function.

Hemodialysis does not alter serum half-life.

Microbiology

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. Cross resistance with other tetracyclines is common.

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 (see INDICATIONS AND USAGE ).

Gram-Negative Bacteria:

Acinetobacter species
Bartonella bacilliformis
Brucella
species
Campylobacter
fetus
Enterobacter aerogenes
Escherichia coli
Francisella tularensis
Haemophilus ducreyi
Haemophilus influenza

Klebsiella granulomatis
Klebsiella
species
Neisseria gonorrhoeae
Shigella
species
Vibrio cholerae
Yersinia pestis

Gram-Positive Bacteria:

Bacillus anthracis
Listeria monocytogenes
Streptococcus pneumoniae

Anaerobes:
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

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 the effectiveness of doxycycline tablets, USP and other antibacterial drugs, doxycycline tablets, 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 Tablets, USP are 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 Tablets, USP are 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 Tablets, USP are 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 Tablets, USP are 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 subspecies pertenue .
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, 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 tablets. 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 tablets 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 tablets 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 tablets in the absence of a  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 tablets should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When doxycycline tablets 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 tablets 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. 1

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. 2

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. 3

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. 4 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 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.

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 WARNINGS and 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/kg of body weight divided into two doses on the first day of treatment, followed by a maintenance dose of 2.2 mg/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.

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, doxycycline may be given with food. Ingestion of a high fat meal has been shown to delay the time to peak plasma concentrations by an average of one hour and 20 minutes. However, in the same study, food enhanced the average peak concentration by 7.5% and the area under the curve by 5.7%.

HOW SUPPLIED

Doxycycline Tablets USP, 50 mg are yellow, round, film coated, tablets, debossed "LCI" on one face and "1335" on the other face. Each tablet contains doxycycline monohydrate equivalent to 50 mg of doxycycline. They are supplied as follows:

Bottles of 100                            NDC 0527-1335-01

Doxycycline Tablets USP, 75 mg are yellow, round, film coated, tablets, debossed "LCI" on one face and "1535" on the other face. Each tablet contains doxycycline monohydrate equivalent to 75 mg of doxycycline. They are supplied as follows:

Bottles of 100                            NDC 0527-1535-01

Doxycycline Tablets USP, 100 mg are yellow, film coated, caplets, debossed "LCI" on one face and "1338" on the other face. Each tablet contains doxycycline monohydrate equivalent to 100 mg of doxycycline. They are supplied as follows:

Bottles of 50                             NDC 0527-1338-50
Bottles of 250                           NDC 0527-1338-25

Doxycycline Tablets USP, 150 mg are yellow, round, film coated, tablets, debossed "LCI" on one face and "1537" on the other face. Each tablet contains doxycycline monohydrate equivalent to 150 mg of doxycycline. They are supplied as follows:

Bottles of 30                             NDC 0527-1537-30
Bottles of 100                           NDC 0527-1537-01

Dispense in a tight light-resistant container with a child-resistant closure.

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

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 4 , and methacycline; in minipigs by doxycycline, minocycline, tetracycline PO 4 , and methacycline; in dogs by doxycycline and minocycline; in monkeys by minocycline.

Minocycline, tetracycline PO 4 , 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. Friedman JM and Polifka JE. Teratogenic Effects of Drugs. A Resource for Clinicians (TERIS) . Baltimore, MD: The Johns Hopkins University Press: 2000:149-195.

  2. Cziezel AE and Rockenbauer M. Teratogenic study of doxycycline. Obstet Gynecol 1997;89:524-528.

  3. Horne HW Jr. and Kundsin RB. The role of mycoplasma among 81 consecutive pregnancies: a prospective study. Int J Fertil 1980; 25:315-317.

  4. Hale T. Medications and Mothers Milk . 9th edition. Amarillo, TX: Pharmasoft Publishing 2000; 225-226.

Distributed by:
Lannett Company, Inc.
Philadelphia, PA 19154

CIB70514D

Rev. 09/18

PRINCIPAL DISPLAY PANEL — 50 mg Tablets

NDC 0527-1335-01

Doxycycline
Tablets, USP

50 mg*

Rx Only

100 TABLETS

Lannett

50 mg 100 count bottle label

PRINCIPAL DISPLAY PANEL — 75 mg Tablets

NDC 0527-1535-01

Doxycycline
Tablets, USP

75 mg*

Rx Only

100 TABLETS

Lannett

75 mg 100 count bottle label

PRINCIPAL DISPLAY PANEL — 100 mg Tablets

NDC 0527-1338-50

Doxycycline
Tablets, USP

100 mg*

Rx Only

50 TABLETS

Lannett

100 mg 50 count bottle label

PRINCIPAL DISPLAY PANEL — 150 mg Tablets

NDC 0527-1537-30

Doxycycline
Tablets, USP

150 mg*

Rx Only

30 TABLETS

Lannett

150 mg 30 count bottle label

DOXYCYCLINE
doxycycline tablet, film coated
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0527-1335
Route of Administration ORAL
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
DOXYCYCLINE (UNII: N12000U13O) (DOXYCYCLINE ANHYDROUS - UNII:334895S862) DOXYCYCLINE ANHYDROUS 50 mg
Inactive Ingredients
Ingredient Name Strength
CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U)
ANHYDROUS LACTOSE (UNII: 3SY5LH9PMK)
STARCH, CORN (UNII: O8232NY3SJ)
MAGNESIUM STEARATE (UNII: 70097M6I30)
SILICON DIOXIDE (UNII: ETJ7Z6XBU4)
POLYVINYL ALCOHOL, UNSPECIFIED (UNII: 532B59J990)
POLYETHYLENE GLYCOLS (UNII: 3WJQ0SDW1A)
TALC (UNII: 7SEV7J4R1U)
TITANIUM DIOXIDE (UNII: 15FIX9V2JP)
D&C YELLOW NO. 10 (UNII: 35SW5USQ3G)
FD&C YELLOW NO. 6 (UNII: H77VEI93A8)
ALUMINUM OXIDE (UNII: LMI26O6933)
Product Characteristics
Color YELLOW Score no score
Shape ROUND Size 8mm
Flavor Imprint Code LCI;1335
Contains
Packaging
# Item Code Package Description Marketing Start Date Marketing End Date
1 NDC:0527-1335-01 100 in 1 BOTTLE, PLASTIC; Type 0: Not a Combination Product 12/08/2005
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA065285 12/08/2005
DOXYCYCLINE
doxycycline tablet, film coated
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0527-1535
Route of Administration ORAL
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
DOXYCYCLINE (UNII: N12000U13O) (DOXYCYCLINE ANHYDROUS - UNII:334895S862) DOXYCYCLINE ANHYDROUS 75 mg
Inactive Ingredients
Ingredient Name Strength
CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U)
ANHYDROUS LACTOSE (UNII: 3SY5LH9PMK)
STARCH, CORN (UNII: O8232NY3SJ)
MAGNESIUM STEARATE (UNII: 70097M6I30)
SILICON DIOXIDE (UNII: ETJ7Z6XBU4)
POLYVINYL ALCOHOL, UNSPECIFIED (UNII: 532B59J990)
POLYETHYLENE GLYCOLS (UNII: 3WJQ0SDW1A)
TALC (UNII: 7SEV7J4R1U)
TITANIUM DIOXIDE (UNII: 15FIX9V2JP)
D&C YELLOW NO. 10 (UNII: 35SW5USQ3G)
FD&C YELLOW NO. 6 (UNII: H77VEI93A8)
ALUMINUM OXIDE (UNII: LMI26O6933)
Product Characteristics
Color YELLOW Score no score
Shape ROUND Size 9mm
Flavor Imprint Code LCI;1535
Contains
Packaging
# Item Code Package Description Marketing Start Date Marketing End Date
1 NDC:0527-1535-01 100 in 1 BOTTLE, PLASTIC; Type 0: Not a Combination Product 08/25/2008
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA065285 08/25/2008
DOXYCYCLINE
doxycycline tablet, film coated
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0527-1338
Route of Administration ORAL
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
DOXYCYCLINE (UNII: N12000U13O) (DOXYCYCLINE ANHYDROUS - UNII:334895S862) DOXYCYCLINE ANHYDROUS 100 mg
Inactive Ingredients
Ingredient Name Strength
CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U)
ANHYDROUS LACTOSE (UNII: 3SY5LH9PMK)
STARCH, CORN (UNII: O8232NY3SJ)
MAGNESIUM STEARATE (UNII: 70097M6I30)
SILICON DIOXIDE (UNII: ETJ7Z6XBU4)
POLYVINYL ALCOHOL, UNSPECIFIED (UNII: 532B59J990)
POLYETHYLENE GLYCOLS (UNII: 3WJQ0SDW1A)
TALC (UNII: 7SEV7J4R1U)
TITANIUM DIOXIDE (UNII: 15FIX9V2JP)
D&C YELLOW NO. 10 (UNII: 35SW5USQ3G)
FD&C YELLOW NO. 6 (UNII: H77VEI93A8)
ALUMINUM OXIDE (UNII: LMI26O6933)
Product Characteristics
Color YELLOW Score no score
Shape OVAL (caplet) Size 13mm
Flavor Imprint Code LCI;1338
Contains
Packaging
# Item Code Package Description Marketing Start Date Marketing End Date
1 NDC:0527-1338-50 50 in 1 BOTTLE, PLASTIC; Type 0: Not a Combination Product 12/08/2005
2 NDC:0527-1338-25 250 in 1 BOTTLE, PLASTIC; Type 0: Not a Combination Product 12/08/2005
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA065285 12/08/2005
DOXYCYCLINE
doxycycline tablet, film coated
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0527-1537
Route of Administration ORAL
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
DOXYCYCLINE (UNII: N12000U13O) (DOXYCYCLINE ANHYDROUS - UNII:334895S862) DOXYCYCLINE ANHYDROUS 150 mg
Inactive Ingredients
Ingredient Name Strength
CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U)
ANHYDROUS LACTOSE (UNII: 3SY5LH9PMK)
STARCH, CORN (UNII: O8232NY3SJ)
MAGNESIUM STEARATE (UNII: 70097M6I30)
SILICON DIOXIDE (UNII: ETJ7Z6XBU4)
POLYVINYL ALCOHOL, UNSPECIFIED (UNII: 532B59J990)
POLYETHYLENE GLYCOLS (UNII: 3WJQ0SDW1A)
TALC (UNII: 7SEV7J4R1U)
TITANIUM DIOXIDE (UNII: 15FIX9V2JP)
D&C YELLOW NO. 10 (UNII: 35SW5USQ3G)
FD&C YELLOW NO. 6 (UNII: H77VEI93A8)
ALUMINUM OXIDE (UNII: LMI26O6933)
Product Characteristics
Color YELLOW Score no score
Shape ROUND Size 11mm
Flavor Imprint Code LCI;1537
Contains
Packaging
# Item Code Package Description Marketing Start Date Marketing End Date
1 NDC:0527-1537-30 30 in 1 BOTTLE, PLASTIC; Type 0: Not a Combination Product 08/25/2008
2 NDC:0527-1537-01 100 in 1 BOTTLE, PLASTIC; Type 0: Not a Combination Product 08/25/2008
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA065285 08/25/2008
Labeler - Lannett Company, Inc. (002277481)
Establishment
Name Address ID/FEI Business Operations
Lannett Company, Inc. 002277481 MANUFACTURE(0527-1335, 0527-1535, 0527-1338, 0527-1537)
Establishment
Name Address ID/FEI Business Operations
Lannett Company, Inc. 829757603 ANALYSIS(0527-1335, 0527-1535, 0527-1338, 0527-1537) , MANUFACTURE(0527-1335, 0527-1535, 0527-1338, 0527-1537)
Establishment
Name Address ID/FEI Business Operations
Lannett Company, Inc. 006422406 LABEL(0527-1335, 0527-1535, 0527-1338, 0527-1537) , PACK(0527-1335, 0527-1535, 0527-1338, 0527-1537)

Revised: 9/2018
Document Id: 7be74936-1840-41a7-9163-a6669ee26106
Set id: 4999bbd9-44ed-4749-9730-be2337bdf490
Version: 22
Effective Time: 20180901
Lannett Company, Inc.