These highlights do not include all the information needed to use DOXYCYCLINE HYCLATE DELAYED-RELEASE TABLETS safely and effectively. See full prescribing information for DOXYCYCLINE HYCLATE DELAYED-RELEASE TABLETS. DOXYCYCLINE HYCLATE delayed-release tablets, for oral use. Initial U.S. Approval: 1967

1 INDICATIONS AND USAGE

INDICATIONS & USAGE SECTION

2 DOSAGE AND ADMINISTRATION

DOSAGE & ADMINISTRATION SECTION

3 DOSAGE FORMS AND STRENGTHS

DOSAGE FORMS & STRENGTHS SECTION

Doxycycline hyclate delayed-release tablets, USP 80 mg are white, oval scored tablets containing yellow pellets and debossed with "D|8" on one face and plain on the other. Each tablet contains specially coated pellets of doxycycline hyclate equivalent to 80 mg of doxycycline. Doxycycline hyclate delayed-release tablets, 200 mg are white, oval scored tablets containing yellow pellets and debossed with "D|D" on one face and plain on the other. Each tablet contains specially coated pellets of doxycycline hyclate equivalent to 200 mg of doxycycline.

4 CONTRAINDICATIONS

CONTRAINDICATIONS SECTION

Doxycycline hyclate delayed-release tablets are contraindicated in persons who have shown hypersensitivity to any of the tetracyclines.

5 WARNINGS AND PRECAUTIONS

WARNINGS AND PRECAUTIONS SECTION

6 ADVERSE REACTIONS

ADVERSE REACTIONS SECTION

7 DRUG INTERACTIONS

DRUG INTERACTIONS SECTION

8 USE IN SPECIFIC POPULATIONS

USE IN SPECIFIC POPULATIONS SECTION

10 OVERDOSAGE

OVERDOSAGE SECTION

In case of overdosage, discontinue medication, treat symptomatically and institute supportive measures. Dialysis does not alter serum half-life and thus would not be of benefit in treating cases of overdosage.

11 DESCRIPTION

DESCRIPTION SECTION

Doxycycline hyclate delayed-release tablets, contain specially coated pellets of doxycycline hyclate, a tetracycline class drug synthetically derived from oxytetracycline, in a delayed-release formulation for oral administration. The structural formula for doxycycline hyclate is: with a molecular formula of C 22 H 24 N 2 O 8 , HCl, ½ C 2 H 6 O, ½ H 2 O and a molecular weight of 512.9. The chemical name for doxycycline hyclate is [4S(4aR,5S,5aR,6R,12aS)]-4-(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,5,10,12,12a-pentahydroxy-6- methyl-1,11-deoxonaphthacene-2-carboxamide monohydrochloride, compound with ethyl alcohol (2:1), monohydrate. Doxycycline hyclate is a yellow crystalline powder soluble in water and in solutions of alkali hydroxides and carbonates. 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. Each tablet contains doxycycline 50 mg, 75 mg, 80 mg, 100 mg, 150 mg or 200 mg (equivalent to doxycycline hyclate 57.7 mg, 86.6 mg, 92.3 mg, 115.4 mg, 173.1 mg or 230.8 mg). Inactive ingredients in the tablet formulation are: lactose monohydrate; microcrystalline cellulose; sodium lauryl sulfate; sodium chloride; talc; anhydrous lactose; corn starch; crospovidone; magnesium stearate; cellulosic polymer coating. Each doxycycline hyclate delayed-release tablets 50 mg tablet contains 3 mg (0.131 mEq) of sodium, each doxycycline hyclate delayed-release tablets 75 mg tablet contains 4.5 mg (0.196 mEq) of sodium, each doxycycline hyclate delayed-release tablets 80 mg tablet contains 4.8 mg (0.209 mEq) of sodium, each doxycycline hyclate delayed-release tablets 100 mg tablet contains 6 mg (0.261 mEq) of sodium, each doxycycline hyclate delayed-release tablets 150 mg tablet contains 9 mg (0.392 mEq) of sodium, and each doxycycline hyclate delayed-release tablets 200 mg tablet contains 12 mg (0.522 mEq) of sodium.

12 CLINICAL PHARMACOLOGY

CLINICAL PHARMACOLOGY SECTION

13 NONCLINICAL TOXICOLOGY

NONCLINICAL TOXICOLOGY SECTION

14 CLINICAL STUDIES

CLINICAL STUDIES SECTION

This was a randomized, double-blind, active-controlled, multicenter trial which enrolled 495 subjects, between 19 to 45 years of age with a confirmed diagnosis of urogenital C. trachomatis infection less than 14 days prior to enrollment, or partner(s) of a subject with a known positive test for urogenital C. trachomatis infection. The primary purpose of this study was to evaluate the efficacy and safety of doxycycline hyclate delayed-release tablets Tablets, 200 mg once daily versus doxycycline hyclate capsules, 100 mg twice daily for seven days for the treatment of uncomplicated urogenital C. trachomatis infection. The primary efficacy objective was to demonstrate non-inferiority of the doxycycline hyclate delayed-release tablets, 200 mg once daily treatment regimen versus the doxycycline 100 mg twice daily treatment regimen for the indication using a negative nucleic acid amplification test (NAAT) at the test of cure visit (day 28) in the mITT population (subjects who were positive at baseline and took at least one day of study drug). Table 2: Primary Efficacy Outcome – Microbiological Cure of C. trachomatis at Day 28 mITT Population Doxycycline hyclate delayed-release tablets, 200 mg once daily Cure Rate (%) Doxycycline hyclate capsules, 100 mg twice daily Cure Rate (%) Difference (%) N 188 190 Microbiological Cure, n (%) 163 (86.7) 171 (90.0) -3.3% 95% Confidence Interval for Cure Rate -10.3, 3.7

15 REFERENCES

REFERENCES SECTION

Friedman JM, Polifka JE. Teratogenic Effects of Drug s. 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. Horne HW Jr. and Kundsin RB. The role of mycoplasma among 81 consecutive pregnancies: a prospective study. Int J Fertil 1980; 25: 315-317. Drugs and Lactation Database (LactMed) [Internet]. Bethesda (MD): National Library of Medicine (US); [Last Revision Date 2015 March 10; cited 2016 Jan]. Doxycycline; LactMed Record Number: 100; [about 3 screens]. Available from: http://toxnet.nlm.nih.gov/newtoxnet/lactmed.htm .

16 HOW SUPPLIED/STORAGE AND HANDLING

HOW SUPPLIED SECTION

Doxycycline hyclate delayed-release tablets, USP, 80 mg are white, oval scored tablets containing yellow pellets and debossed with "D|8" on one face and plain on the other. Each tablet contains specially coated pellets of doxycycline hyclate equivalent to 80 mg of doxycycline. Bottles of 30 tablets NDC 51862-571-30 Doxycycline hyclate delayed-release tablets, 200 mg are white, oval scored tablets containing yellow pellets and debossed with "D|D" on one face and plain on the other. Each tablet contains specially coated pellets of doxycycline hyclate equivalent to 200 mg of doxycycline. Bottles of 30 tablets Bottles of 60 tablets NDC 68308-716-30 NDC 68308-716-60

17 PATIENT COUNSELING INFORMATION

INFORMATION FOR PATIENTS SECTION

Advise patients taking doxycycline for malaria prophylaxis: that no present-day antimalarial agent, including doxycycline, guarantees protection against malaria. to avoid being bitten by mosquitoes by using personal protective measures that help avoid contact with mosquitoes, especially from dusk to dawn (for example, staying in well-screened areas, using mosquito nets, covering the body with clothing, and using an effective insect repellent). that doxycycline prophylaxis: should begin 1 to 2 days before travel to the malarious area, should be continued daily while in the malarious area and after leaving the malarious area, should be continued for 4 further weeks to avoid development of malaria after returning from an endemic area, should not exceed 4 months. Advise all patients taking doxycycline: to avoid excessive sunlight or artificial ultraviolet light while receiving doxycycline and to discontinue therapy if phototoxicity (for example, skin eruptions, etc.) occurs. Sunscreen or sunblock should be considered [ see Warnings and Precautions (5.3) ]. to drink fluids liberally along with doxycycline to reduce the risk of esophageal irritation and ulceration [ see Adverse Reactions (6.1) ]. that the absorption of tetracyclines is reduced when taken with foods, especially those that contain calcium. However, the absorption of doxycycline is not markedly influenced by simultaneous ingestion of food or milk [ see Drug Interactions (7.3) ]. that the absorption of tetracyclines is reduced when taken with antacids containing aluminum, calcium or magnesium, bismuth subsalicylate, and iron-containing preparations [ see Drug Interactions (7.3) ]. that the use of doxycycline might increase the incidence of vaginal candidiasis. Advise patients that diarrhea is a common problem caused by antibacterials which usually ends when the antibacterial is discontinued. Sometimes after starting treatment with antibacterials, 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 antibacterial. If this occurs, patients should contact their physician as soon as possible. Patients should be counseled that antibacterial drugs including doxycycline hyclate delayed-release tablets should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When doxycycline hyclate delayed-release tablets is 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 hyclate delayed-release tablets or other antibacterial drugs in the future.

FDA-Approved Patient Labeling Doxycycline hyclate delayed-release tablets, 50 mg, 75 mg, 80 mg, 100 mg, 150 mg and 200 mg Instructions for Breaking the 150 mg Doxycycline hyclate delayed-release dual-scored tablet

SPL PATIENT PACKAGE INSERT SECTION

Your doctor may find it necessary to adjust your dosage of doxycycline hyclate delayed-release tablets to obtain the proper treatment response. The tablet is marked with separation lines (score lines) and may be broken at these score lines to provide any of the following doses. If your doctor prescribed: 150 mg treatment (take the entire tablet) 100 mg treatment (take two thirds of the tablet or two 50 mg tablet segments) 50 mg treatment (take one third of the tablet) To break the tablet, hold the tablet between your thumbs and index fingers close to the appropriate score line. Then, with the score line facing you, apply enough pressure to snap the tablet segments apart (do not use segments that do not break along the score line). Distributed by: Mayne Pharma Raleigh, NC 27609 61449

PRINCIPAL DISPLAY PANEL - 75 mg Tablet Bottle Label

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

NDC 68308-775-60 Doxycycline Hyclate Delayed-Release Tablets, USP Do not chew or crush tablets. Each tablet contains specially coated pellets of doxycycline hyclate equivalent to 75 mg of doxycycline. 75 mg Rx Only mayne pharma 60 Tablets

PRINCIPAL DISPLAY PANEL - 100 mg Tablet Bottle Label

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

NDC 68308-710-10 Doxycycline Hyclate Delayed-Release Tablets, USP Do not chew or crush tablets. Each tablet contains specially coated pellets of doxycycline hyclate equivalent to 100 mg of doxycycline. 100 mg Rx Only mayne pharma 100 Tablets

PRINCIPAL DISPLAY PANEL - 150 mg Tablet Bottle Label

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

NDC 68308-715-10 Doxycycline Hyclate Delayed-Release Tablets, USP Do not chew or crush tablets. Each tablet contains specially coated pellets of doxycycline hyclate equivalent to 150 mg of doxycycline. 150 mg Rx Only mayne pharma 100 Tablets

PRINCIPAL DISPLAY PANEL - 200 mg Tablet Bottle Label

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

NDC 68308-716-30 Doxycycline Hyclate Delayed-Release Tablets, USP Do not chew or crush tablets. Each tablet contains specially coated pellets of doxycycline hyclate equivalent to 200 mg of doxycycline. 200 mg Rx Only mayne pharma 30 Tablets