Doxycycline

INDICATIONS AND USAGE To reduce the development of drug-resistant bacteria and maintain 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 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 Chlamydia 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 Calymmatobacterium 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.

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.

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

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, erythema multiforme, and fixed drug eruption 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. Psychiatric: Depression, anxiety, suicidal ideation, insomnia, abnormal dreams, hallucination Other: Intracranial hypertension (IH, pseudotumor cerebri) has been associated with the use of tetracyclines (s ee 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 Strides Pharma Inc. at 1-877-244-9825 or go to www.strides.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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.

DESCRIPTION Doxycycline, USP is a broad-spectrum antibacterial synthetically derived from oxytetracycline. Doxycycline 150 mg, 100 mg, 75 mg and 50 mg tablets contain doxycycline monohydrate equivalent to 150 mg, 100 mg, 75 mg or 50 mg of doxycycline for oral administration. The chemical designation of the light-yellow crystalline powder is alpha-6-deoxy-5-oxytetracycline. Structural formula: C 22 H 24 N 2 O 8 •H 2 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. Inactive ingredients include colloidal silicon dioxide, FD&C yellow #6, magnesium stearate, microcrystalline cellulose, sodium starch glycolate, and titanium dioxide. In addition, Doxycycline 100 mg and 50 mg tablets contain hypromellose 3cP, hypromellose 6cP, D&C yellow #10 lake, polyethylene glycol 400, polysorbate 80; Doxycycline 75 mg and 150 mg tablets contain hypromellose 15cP, lactose monohydrate, yellow iron oxide and triethyl citrate. Its molecular weight is 462.46. this is the structure

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.

HOW SUPPLIED Doxycycline Tablets 50 mg are a peach colored, film coated round biconvex tablets, debossed with 'I61' on one side and plain on the other side. Each tablet contains doxycycline monohydrate equivalent to 50 mg of doxycycline. They are supplied as follows: Doxycycline Tablets 50 mg Blister Package of 10 NDC 23155-133-11 Carton of 30 (3 x 10 tablets) NDC 23155-133-30 Bottles of 100 NDC 23155-133-01 Bottles of 500 NDC 23155-133-05 Doxycycline Tablets 75 mg are a peach colored, film coated, capsule shaped, biconvex tablets, debossed with 'I62' on one side and plain on the other side. Each tablet contains doxycycline monohydrate equivalent to 75 mg of doxycycline. They are supplied as follows: Doxycycline Tablets 75 mg Blister Package of 10 NDC 23155-134-11 Carton of 30 (3 x 10 tablets) NDC 23155-134-30 Bottles of 100 NDC 23155-134-01 Bottles of 500 NDC 23155-134-05 Doxycycline Tablets 100 mg are a peach colored, film coated, round biconvex tablets, debossed with 'I63' on one side and plain on the other side. Each tablet contains doxycycline monohydrate equivalent to 100 mg of doxycycline. They are supplied as follows: Doxycycline Tablets 100 mg Blister Package of 10 NDC 23155-135-11 Carton of 30 (3 x 10 tablets) NDC 23155-135-30 Bottles of 50 NDC 23155-135-25 Bottles of 500 NDC 23155-135-05 Doxycycline Tablets 150 mg are a peach colored, film coated capsule shaped scored tablets, debossed with 'I' and '64' on either side of a breakline and plain on other side. Each tablet contains doxycycline monohydrate equivalent to 150 mg of doxycycline. They are supplied as follows: Doxycycline Tablets 150 mg Blister Package of 10 NDC 23155-136-11 Carton of 30 (3 x 10 tablets) NDC 23155-136-30 Bottles of 30 NDC 23155-136-03 Bottles of 500 NDC 23155-136-05 STORE AT 20° to 25°C (68° to 77°F). [SEE USP CONTROLLED ROOM TEMPERATURE.] PROTECT FROM LIGHT. DISPENSE IN A TIGHT LIGHT-RESISTANT CONTAINER AS DEFINED IN THE USP/NF.