Doxycycline Hyclate

RECENT MAJOR CHANGES Warnings and Precautions, Severe Skin Reactions ( 5.5 ) 3/2025

1 INDICATIONS AND USAGE Doxycycline hyclate tablet is a tetracycline class drugs indicated for: Rickettsial infections ( 1.1 ) Sexually transmitted infections ( 1.2 ) Respiratory tract infections ( 1.3 ) Specific bacterial infections ( 1.4 ) Ophthalmic infections ( 1.5 ) Anthrax, including inhalational anthrax (post-exposure) ( 1.6 ) Alternative treatment for selected infections when penicillin is contraindicated ( 1.7 ) Adjunctive therapy for acute intestinal amebiasis and severe acne ( 1.8 ) Prophylaxis of malaria ( 1.9 ) To reduce the development of drug-resistant bacteria and maintain the effectiveness of doxycycline hyclate tablets and other antibacterial drugs, doxycycline hyclate tablets should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. ( 1.10 ) 1.1 Rickettsial Infections Doxycycline hyclate tablets are indicated for treatment of Rocky Mountain spotted fever, typhus fever and the typhus group, Q fever, rickettsial pox, and tick fevers caused by Rickettsiae . 1.2 Sexually Transmitted Infections Doxycycline hyclate tablets are indicated for treatment of the following sexually transmitted infections: Uncomplicated urethral, endocervical or rectal infections caused by Chlamydia trachomatis . Nongonococcal urethritis caused by Ureaplasma urealyticum . Lymphogranuloma venereum caused by Chlamydia trachomatis . Granuloma inguinale caused by Klebsiella granulomatis . Uncomplicated gonorrhea caused by Neisseria gonorrhoeae . Chancroid caused by Haemophilus ducreyi . 1.3 Respiratory Tract Infections Doxycycline hyclate tablets are indicated for treatment of the following respiratory tract infections: Respiratory tract infections caused by Mycoplasma pneumoniae . Psittacosis (ornithosis) caused by Chlamydophila psittaci . 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 microorganisms, when bacteriological testing indicates appropriate susceptibility to the drug: Respiratory tract infections caused by Haemophilus influenzae . Respiratory tract infections caused by Klebsiella species . Upper respiratory infections caused by Streptococcus pneumoniae . 1.4 Specific Bacterial Infections Doxycycline hyclate tablets are indicated for treatment of the following specific bacterial infections: Relapsing fever due to Borrelia recurrentis . 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. Because many strains of the following groups of microorganisms have been shown to be resistant to doxycycline, culture and susceptibility testing are recommended. Doxycycline hyclate tablets are indicated for treatment of infections caused by the following gram-negative microorganisms, when bacteriological testing indicates appropriate susceptibility to the drug: Escherichia coli Enterobacter aerogenes Shigella species Acinetobacter species Urinary tract infections caused by Klebsiella species. 1.5 Ophthalmic Infections Doxycycline hyclate tablets are indicated for treatment of the following ophthalmic infections: Trachoma caused by Chlamydia trachomatis , although the infectious agent is not always eliminated as judged by immunofluorescence. Inclusion conjunctivitis caused by Chlamydia trachomatis . 1.6 Anthrax Including Inhalational Anthrax (Post-Exposure) Doxycycline hyclate tablets are indicated for the treatment of Anthrax due to Bacillus anthracis , including inhalational anthrax (post-exposure); to reduce the incidence or progression of disease following exposure to aerosolized Bacillus anthracis . 1.7 Alternative Treatment for Selected Infections when Penicill …

2 DOSAGE AND ADMINISTRATION ● Important Administration Instructions for Doxycycline Hyclate Tablets Doxycycline hyclate tablets (150 mg) can be broken into two-thirds or one-third to provide a 50 mg and 100 mg strength, respectively. ( 2.1 ) ● Dosage in Adults for Doxycycline Hyclate Tablets : The usual dosage is 200 mg on the first day of treatment (administered 100 mg every 12 hours) followed by a maintenance dose of 100 mg daily. ( 2.1 ) In the management of more severe infections (particularly chronic infections of the urinary tract), 100 mg every 12 hours is recommended. ( 2.1 ) ● Dosage in Pediatric Patients for Doxycycline Hyclate Tablets : For all pediatric patients weighing less than 45 kg with severe or life-threatening infections (e.g., anthrax, Rocky Mountain spotted fever), the recommended dose is 2.2 mg per kg of body weight administered every 12 hours. Pediatric patients weighing 45 kg or more should receive the adult dose. ( 2.3 ) For pediatric patients with less severe disease (greater than 8 years of age and weighing less than 45 kg), the recommended dose 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 two doses. For pediatric patients weighing over 45 kg, the usual adult dose should be used. (2.3) See Full Prescribing Information for additional indication specific dosage information and important administration instructions for doxycycline hyclate tablets. ( 2.1 , 2.4 , 2.5 ) 2.1 Important Administration Instructions The usual dosage and frequency of administration of doxycycline hyclate tablets differs from that of the other tetracyclines. Exceeding the recommended dosage may result in an increased incidence of adverse reactions. Administer doxycycline hyclate tablets with adequate amounts of fluid to wash down the drugs and reduce the risk of esophageal irritation and ulceration [see Adverse Reactions ( 6 )] . If gastric irritation occurs, doxycycline hyclate tablets may be given with food or milk [see Clinical Pharmacology ( 12.3 )] Doxycycline hyclate tablets (150 mg) can be broken into two-thirds or one-third to provide a 100 mg and 50 mg strength, respectively [see FDA-approved patient labeling ] . 2.2 Dosage in Adult Patients ● The usual dosage of doxycycline hyclate tablets is 200 mg on the first day of treatment (administered 100 mg every 12 hours) followed by a maintenance dose of 100 mg daily. 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. ● For certain selected specific indications, the recommended duration or dosage and duration of doxycycline hyclate tablets in adult patients are as follows: Streptococcal infections, therapy should be continued for 10 days. Uncomplicated urethral, endocervical, or rectal infection caused by Chlamydia trachomatis : 100 mg by mouth twice-a-day for 7 days. 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. Nongonococcal urethritis (NGU) caused by C. trachomatis and U. urealyticum : 100 mg by mouth twice-a-day for 7 days. Syphilis - early: Patients who are allergic to penicillin should be treated with doxycycline 100 mg by mouth twice-a-day for 2 weeks. Syphilis of more than one year's duration: Patients who are allergic to penicillin should be treated with doxycycline 100 mg by mouth twice-a-day for 4 weeks. Acute epididymo-orchitis caused by N. gonorrhoeae : 100 mg by mouth, twice-a-day for at least 10 days. Acute epididymo-orchitis caused by C. trachomatis : 100 mg, by mouth, twice-a-day for at least 10 days. 2.3 Dosage in Pediatric Patients For all pediatric patient …

3 DOSAGE FORMS AND STRENGTHS Doxycycline hyclate tablets USP: 75 mg and 150 mg (functionally scored) ( 3 ) Doxycycline Hyclate Tablets USP: Doxycycline Hyclate Tablets USP, 75 mg are light-teal, round, biconvex, film-coated tablets debossed with "LU" on one side and "C80" on the other side (each tablet contains 75 mg doxycycline as 86.6 mg doxycycline hyclate). Doxycycline Hyclate Tablets USP, 150 mg are mossy-green, capsule-shaped, biconvex, film-coated tablets, scored on both sides. Each side of the functionally scored tablet has two parallel score line for splitting into 3 equal portions with "C" debossed on each portion of one side of the tablet, and plain on the other side (each tablet contains 150 mg doxycycline as 173.2 mg doxycycline hyclate).

4 CONTRAINDICATIONS Doxycycline hyclate is contraindicated in persons who have shown hypersensitivity to any of the tetracyclines. ( 4 ) Doxycycline hyclate is contraindicated in persons who have shown hypersensitivity to any of the tetracyclines.

6 ADVERSE REACTIONS Adverse reactions observed in patients receiving tetracyclines include anorexia, nausea, vomiting, diarrhea, rash, photosensitivity, urticaria, and hemolytic anemia. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Lupin Pharmaceuticals, Inc. at 1-800-399-2561, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. The following adverse reactions have been identified during clinical trials or post-approval use of tetracycline-class drugs, including doxycycline. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Gastrointestinal Anorexia, nausea, vomiting, diarrhea, glossitis, dysphagia, enterocolitis, 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. Superficial discoloration of the adult permanent dentition, reversible upon drug discontinuation and professional dental cleaning has been reported. Permanent tooth discoloration and enamel hypoplasia may occur with drugs of the tetracycline class when used during tooth development [See Warnings and Precautions ( 5.1 )]. 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 ( 2.1 )]. Skin Maculopapular and erythematous rashes, Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis, and erythema multiforme, and fixed drug eruption have been reported. Photosensitivity has been reported [see Warnings and Precautions (5.3 )] Renal Rise in BUN has been reported and is apparently dose-related [see Warnings and Precautions ( 5.7 )]. Hypersensitivity reactions Urticaria, angioneurotic edema, anaphylaxis, anaphylactoid purpura, serum sickness, pericarditis, exacerbation of systematic lupus erythematosus and drug reaction with eosinophilia and systematic symptoms (DRESS). Blood Hemolytic anemia, thrombocytopenia, neutropenia, and eosinophilia have been reported. Intracranial Hypertension Intracranial hypertension (IH, pseudotumor cerebri) has been associated with the use of tetracyclines [see Warnings and Precautions ( 5.6 )]. Thyroid Gland Changes When given over prolonged periods, tetracyclines have been reported to produce brown-black microscopic discoloration of thyroid glands. No abnormalities of thyroid function are known to occur. Psychiatric: Depression, anxiety, suicidal ideation, insomnia, abnormal dreams, hallucination.

7 DRUG INTERACTIONS Patients who are on anticoagulant therapy may require downward adjustment of their anticoagulant dosage. ( 7.1 ) Avoid co-administration of tetracyclines with penicillin. ( 7.2 ) Absorption of tetracyclines, including doxycycline hyclate is impaired by antacids containing aluminum, calcium, or magnesium, bismuth subsalicylate and iron-containing preparations. ( 7.3 ) Concurrent use of tetracyclines, including doxycycline hyclate may render oral contraceptives less effective. ( 7.4 ) Barbiturates, carbamazepine and phenytoin decrease the half-life of doxycycline. ( 7.5 ) 7.1 Anticoagulant Drugs Because tetracyclines have been shown to depress plasma prothrombin activity, patients who are on anticoagulant therapy may require downward adjustment of their anticoagulant dosage. 7.2 Penicillin Since bacteriostatic drugs may interfere with the bactericidal action of penicillin, it is advisable to avoid giving tetracyclines, including doxycycline hyclate in conjunction with penicillin. 7.3 Antacids and Iron Preparations Absorption of tetracyclines, including doxycycline hyclate is impaired by antacids containing aluminum, calcium, or magnesium, bismuth subsalicylate, and iron-containing preparations. 7.4 Oral Contraceptives Concurrent use of tetracyclines, including doxycycline hyclate may render oral contraceptives less effective. 7.5 Barbiturates and Anti-Epileptics Barbiturates, carbamazepine, and phenytoin decrease the half-life of doxycycline. 7.7 Drug and Laboratory Test Interactions False elevations of urinary catecholamines may occur due to interference with the fluorescence test.

8 USE IN SPECIFIC POPULATIONS Lactation: Breastfeeding is not recommended. ( 8.2 ) 8.1 Pregnancy Risk Summary Doxycycline hyclate, like other tetracycline-class antibacterial drugs, may cause discoloration deciduous teeth, and reversible inhibition of bone growth when administered during the second and third trimester of pregnancy [see Warnings and Precautions ( 5.1 ) and ( 5.2 )]. Available data from published studies over decades have not shown a difference in major birth defect risk compared to unexposed pregnancies with doxycycline exposure in the first trimester of pregnancy (see Data). There are no available data on the risk of miscarriage following exposure to doxycycline in pregnancy. Advise the patient of the potential risk to the fetus if doxycycline hyclate is used during pregnancy. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Human Data: A retrospective cohort study of 1,690 pregnant patients who received doxycycline prescriptions in the first trimester of pregnancy compared to an unexposed pregnant cohort showed no difference in the major malformation rate. There is no information on the dose or duration of treatment, or if the patients actually ingested the doxycycline that was prescribed. Other published studies on exposure to doxycycline in the first trimester of pregnancy have small sample sizes; however, these studies have not shown an increased risk of major malformations. The use of tetracyclines during tooth development (second and third trimester of pregnancy) may cause permanent discoloration of the teeth (yellow-gray-brown). This adverse reaction is more common during long-term use of the drug but has been observed following repeated short-term courses. [see Warnings and Precautions ( 5.1 , 5.2 )] . Animal Data: 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 embryotoxicity also has been noted in animals treated early in pregnancy 8.2 Lactation Risk Summary Based on available published data, doxycycline is present in human milk. There are no data that inform the levels of doxycycline in breastmilk, the effects on the breastfed infant, or the effects on milk production. Because of the potential for serious adverse reactions, including tooth discoloration and inhibition of bone growth, advise patients that breastfeeding is not recommended during treatment with doxycycline hyclate and for 5 days after the last dose. 8.3 Females and Males of Reproductive Potential Infertility Based on findings from a fertility study in animals, doxycycline may impair female and male fertility. The reversibility of this finding is unclear. [see Nonclinical Toxicology ( 13.1 )]. 8.4 Pediatric Use Because of the effects of drugs of the tetracycline-class on tooth development and growth, use doxycycline hyclate 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 Precautions ( 5.1 , 1.1 ) and Dosage and Administration ( 2.1 , 2.5 )] . 8.5 Geriatric Use Clinical studies of doxycycline hyclate tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. Doxycycline Hyclate Tablets each contains less than 1 mg of sod …

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 Tablets. Gram-Negative Bacteria Acinetobacter species Bartonella bacilliformis Brucella species Klebsiella species Klebsiella granulomatis Campylobacter fetus Enterobacter aerogenes Escherichia coli Francisella tularensis Haemophilus ducreyi Haemophilus influenzae 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 .

11 DESCRIPTION Doxycycline Hyclate Tablets USP contain doxycycline hyclate, a tetracycline class drug synthetically derived from oxytetracycline, in an immediate release formulation for oral administration. The molecular formula of doxycycline hyclate is (C 22 H 24 N 2 O 8 ●HCl) 2 ●C 2 H 6 O●H 2 O and the molecular weight of doxycycline hyclate is 1025.87. The chemical name for doxycycline hyclate 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 monohydrochloride, compound with ethyl alcohol (2:1), monohydrate. The structural formula for doxycycline hyclate is: Figure 1: Structure of Doxycycline Hyclate Doxycycline hyclate is a yellow crystalline powder soluble in water and in solutions of alkali hydroxides and carbonates. Doxycycline Hyclate Tablets USP: Doxycycline hyclate tablets USP are available as 75 mg and 150 mg tablets. Each 75 mg tablet contains 86.6 mg of doxycycline hyclate equivalent to 75 mg of doxycycline. Each 150 mg tablet contains 173.2 mg of doxycycline hyclate equivalent to 150 mg of doxycycline. Inactive ingredients in the tablet formulation are: croscarmellose sodium, hypromellose, magnesium stearate, microcrystalline cellulose and sodium lauryl sulfate. Film-coating contains: FD & C Blue # 1 / Brilliant Blue FCF Aluminum Lake (75 mg Tablet), FD & C Yellow # 6 /Sunset Yellow FCF Aluminum Lake (75 mg Tablet), FD & C Blue #2 / Indigo Carmine AL (150 mg Tablet), iron oxide yellow (150 mg Tablet), polyethylene glycol, polyvinyl alcohol, talc, titanium dioxide. Doxycycline hyclate tablets USP, 75 mg contain 0.34 mg (0.0146 mEq) of sodium. Doxycycline hyclate tablets USP, 150 mg contain 0.68 mg (0.0295 mEq) of sodium. Doxycycline hyclate tablets USP meets USP Dissolution Test 3. image-1

10 OVERDOSAGE 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.

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied Doxycycline Hyclate Tablets USP, 75 mg are light-teal, round, biconvex, film-coated tablets debossed with "LU" on one side and "C80" on the other side. Each 75 mg tablet contains 86.6 mg of doxycycline hyclate equivalent to 75 mg of doxycycline. Bottles of 30 tablets: NDC 68180-653-06 Bottles of 60 tablets: NDC 68180-653-07 Bottles of 90 tablets: NDC 68180-653-09 Doxycycline Hyclate Tablets USP, 150 mg are mossy-green, capsule-shaped, biconvex, film-coated tablets scored on both sides. Each side of the functionally scored tablet has two parallel score line for splitting into 3 equal portions with "C" debossed on each portion of one side of the tablet, and plain on the other side. Each 150 mg tablet contains 173.2 mg of doxycycline hyclate equivalent to 150 mg of doxycycline. Bottles of 30 tablets: NDC 68180-654-06 Bottles of 60 tablets: NDC 68180-654-07 Bottles of 90 tablets: NDC 68180-654-09 Storage Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature]. Protect from light and moisture. Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.