鹽酸多西環(huán)素緩釋片F(xiàn)DA說(shuō)明書-

1、_HIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed to use DORYX (doxycycline hyclate delayed-release tablets safely and effectively. See Full Prescribing Information for DORYX Tablets. DORYX (doxycycline hyclate delayed-release tablets, 80 mg, 100 mg, 15

2、0 mg, and 200 mg for Oral use. Initial U.S. Approval: 1967 To reduce the development of drug-resistant bacteria and maintain the effectiveness of doxycycline hyclate and other antibacterial drugs, DORYX Tablets should be used only to treat or prevent infections that are proven or strongly suspected

3、to be caused by bacteria. (1 -RECENT MAJOR CHANGES- Dosage and Administration (2.1 04/2013 -INDICATIONS AND USAGE-DORYX is a tetracycline-class antimicrobial indicated for: Rickettsial infections (1.1 Sexually transmitted infections (1.2 Respiratory tract infections (1.3 Specific bacterial infection

4、s (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 in acute intestinal amebiasis and severe acne (1.8 Prophylaxis of malaria (1.9 -DOSAGE AND ADMINISTRA

5、TION- Adults: the usual dose of oral doxycycline is 200 mg on the first day oftreatment (administered 100 mg every 12 hours followed by amaintenance dose of 100 mg daily. In the management of more severe infections (particularly chronic infections of the urinary tract, 100 mg every 12 hours is recom

6、mended. (2.1 For children above eight years of age: The recommended dosage schedule for children weighing 45 kg or less is 4.4 mg/kg of body weight divided into two doses on the first day of treatment, followed by 2.2 mg/kg of body weight given as a single daily dose or divided into two doses on sub

7、sequent days. For more severe infections up to 4.4 mg/kg of body weight may be used. For children over 45 kg, the usual adult dose should be used. (2.1 -DOSAGE FORMS AND STRENGTHS- Tablets: 80 mg, 100 mg, 150 mg, and 200 mg (3 -CONTRAINDICATIONS-Doxycycline is contraindicated in persons who have sho

8、wn hypersensitivity to any of the tetracyclines. (4 -WARNINGS AND PRECAUTIONS- The use of drugs of the tetracycline-class 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. (5.1 Clostridium

9、difficile -associated diarrhea: Evaluate patients if diarrhea occurs. (5.2 Photosensitivity manifested by an exaggerated sunburn reaction has been observed in some individuals taking tetracyclines. Limit sun exposure. (5.3 Overgrowth of non-susceptible organisms, including fungi, may occur. Reevalua

10、te therapy if superinfection occurs. (5.4 -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 Warner Chilcott at 1-80

11、0-521-8813 or FDA at 1-800-FDA-1088 or /medwatch . -DRUG INTERACTIONS- Patients who are on anticoagulant therapy may require downward adjustment of their anticoagulant dosage (7.1 Avoid coadministration of tetracyclines with penicillin (7.2 Absorption of tetracyclines is impaired by antac

12、ids containing aluminum, calcium, or magnesium, bismuth subsalicylate and iron-containing preparations (7.3 Concurrent use of tetracycline may render oral contraceptives less effective (7.4 Barbiturates, carbamazepine and phenytoin decrease the half-life of doxycycline (7.5 -USE IN SPECIFIC POPULATI

13、ONS- Pregnancy Category D (8.1 Tetracyclines are excreted in human milk; however, the extent of absorption of doxycycline in the breastfed infant is not known. Doxycycline use during nursing should be avoided if possible. (8.3 See 17 for PATIENT COUNSELING INFORMATION and FDA-approved Patient Labeli

14、ng . Revised: 04/2013 FULL PRESCRIBING INFORMATION: CONTENTS* 1 INDICATIONS AND USAGE 1.1 R ickettsial infections 1.2 Sexually transmitted infections 1.3 Respiratory tract infections 1.4 Specific bacterial infections 1.5 Ophthalmic infections1.6 Anthrax, including inhalational anthrax (post-exposure

15、 1.7 Alternative treatment for selected infections when penicillin iscontraindicated1.8 Adjunctive therapy for acute intestinal amebiasis and severe acne 1.9 Prophylaxis of malaria 2 DOSAGE AND ADMINISTRATION2.1 Usual Dosage and Administration 2.2 For prophylaxis of malaria 2.3 Inhalation anthrax (p

16、ost exposure 2.4 Sprinkling the tablet over applesauce3 DOSAGE FORMS AND STRENGTHS4 CONTRAINDICATIONS5 WARNINGS AND PRECAUTIONS5.1 T ooth Development 5.2 Clostridium difficile associated diarrhea 5.3 Photosensitivity 5.4 Superinfection 5.5 Benign Intracranial Hypertension 5.6 Skeletal Development 5.

17、7 Antianabolic Action 5.8 Malaria 5.9 Development of Drug-Resistant Bacteria 5.10 Laboratory Monitoring for Long-Term Therapy 6 ADVERSE REACTIONS6.1 Clinical Trial Experience 6.2 Postmarketing Experience 7 DRUG INTERACTIONS7.1 A nticoagulant Drugs 7.2 Penicillin 7.3 Antacids and Iron Preparations 7.

18、4 Oral Contraceptives 7.5 Barbiturates and Anti-epileptics 7.6 Penthrane 7.7 Drug/Laboratory Test Interactions 8 USE IN SPECIFIC POPULATIONS8.1 P regnancy 8.3 Nursing Mothers 8.4 Pediatric Use 8.5 Geriatric Use 10 OVERDOSAGE 11 DESCRIPTION 12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action 12.3 Pharm

19、acokinetics 12.4 Microbiology 13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 13.2 Animal Toxicology and/or Pharmacology 14 CLINICAL STUDIES 15 REFERENCES16 HOW SUPPLIED/STORAGE AND HANDLING 17 PATIENT COUNSELING INFORMATION 17.1 Instructions for breaking the 150

20、mg Dual-Scored Tablet FDA-Approved Patient Labeling*Sections or subsections omitted from the Full Prescribing Information are not listed.1 INDICATIONS AND USAGETo reduce the development of drug-resistant bacteria and maintain the effectiveness of DORYX and other antibacterial drugs, DORYX should be

21、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 a

22、nd susceptibility patterns may contribute to the empiric selection of therapy.Doxycycline is a tetracycline-class antimicrobial indicated in the following conditions or diseases:1.1 RickettsialinfectionsRocky Mountain spotted fever, typhus fever and the typhus group, Q fever, rickettsialpox, and tic

23、k fevers caused by Rickettsiae.1.2 Sexually transmitted infectionsUncomplicated 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

24、 Calymmatobacterium granulomatis. Uncomplicated gonorrhea caused by Neisseria gonorrhoeae.Chancroid caused by Haemophilus ducreyi.infections1.3 RespiratorytractRespiratory tract infections caused by Mycoplasma pneumoniae.Psittacosis (ornithosis caused by Chlamydophila psittaci.Because many strains o

25、f 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

26、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 infectionsRelapsing fever due to Borrelia recurrentis.Plague due to Yersinia pes

27、tis.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

28、 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 bacteriological testing indicates appropriate susceptibility to the d

29、rug:Escherichia coliEnterobacter aerogenesShigella speciesAcinetobacter speciesUrinary tract infections caused by Klebsiella species.infections1.5 O phthalmicTrachoma caused by Chlamydia trachomatis, although the infectious agent is not always eliminated as judged by immunofluorescence.Inclusion con

30、junctivitis caused by Chlamydia trachomatis.1.6 Anthrax including inhalational anthrax (post-exposureAnthrax 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 Alternativ

31、e treatment for selected infections when penicillin iscontraindicatedWhen penicillin is contraindicated, doxycycline is an alternative drug in the treatment of the following infections:Syphilis caused by Treponema pallidum.Yaws caused by Treponema pertenue.Vincents infection caused by Fusobacterium

32、fusiforme.Actinomycosis caused by Actinomyces israelii.Infections caused by Clostridium species.1.8 Adjunctive therapy for acute intestinal amebiasis and severe acneIn acute intestinal amebiasis, doxycycline may be a useful adjunct to amebicides.In severe acne, doxycycline may be useful adjunctive t

33、herapy.1.9 Prophylaxis of malariaDoxycycline is indicated for the prophylaxis of malaria due to Plasmodium falciparum in short-term travelers (less than 4 months to areas with chloroquine and/or pyrimethamine-sulfadoxine resistant strains see Dosage and Administration (2.2 and Patient Counseling Inf

34、ormation (17.2 DOSAGE AND ADMINISTRATION2.1 Usual Dosage and AdministrationTHE 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 ora

35、l doxycycline 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 infection

36、s of the urinary tract, 100 mg every 12 hours is recommended.For pediatric patients above eight years of age: The recommended dosage schedule for children weighing 45 kg or less is 4.4 mg/kg of body weight divided into two doses on the first day of treatment, followed by 2.2 mg/kg of body weight giv

37、en as a single daily dose or divided into two doses on subsequent days. For more severe infections up to 4.4 mg/kg of body weight may be used. For children over 45 kg, the usual adult dose should be used.Administration of adequate amounts of fluid along with capsule and tablet forms of drugs in the

38、tetracycline-class is recommended to wash down the drugs and reduce the risk of esophageal irritation and ulceration see Adverse Reactions (6.1.If gastric irritation occurs, doxycycline may be given with food or milk see Clinical Pharmacology (12.When used in streptococcal infections, therapy should

39、 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. As an alternate dosing regimen for uncomplicated urethral or endocervical infection caused by Chlamydia trachomatis, administer 200 mg by mouth

40、 once-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 U. urealy

41、ticum: 100 mg by mouth twice-aday 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 years duration: Patients who are allergic to penicillin should be treated with doxycycline 100 mg

42、by mouth twice-a-day for 4 weeks.Acute epididymo-orchitis caused by C. trachomatis: 100 mg, by mouth, twice-a-day for at least 10 days.2.2 For prophylaxis of malariaFor adults, the recommended dose is 100 mg daily. For children over 8 years of age, the recommended dose is 2 mg/kg given once daily up

43、 to the adult dose. Prophylaxis should begin 1 or 2 days before travel to the malarious area. Prophylaxis should be continued daily during travel in the malarious area and for 4 weeks after the traveler leaves the malarious area.2.3 Inhalational anthrax (post-exposureADULTS: 100 mg, of doxycycline,

44、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.2.4 Sprinkling the tablet over applesauceDORYX Tablets may also be administered by carefully breaking up t

45、he tablet and sprinkling the tablet contents (delayed-release pellets on a spoonful of applesauce. The delayed-release pellets must not be crushed or damaged when breaking up the tablet. Any loss of pellets in the transfer would prevent using the dose. The applesauce/DORYX mixture should be swallowe

46、d immediately without chewing and may be followed by a glass of water if desired. The applesauce should not be hot, and it should be soft enough to be swallowed without chewing. In the event that a prepared dose ofapplesauce/DORYX Tablet cannot be taken immediately, the mixture should be discarded a

47、nd not stored for later use.3 DOSAGE FORMS AND STRENGTHSDORYX (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 hyc

48、late equivalent to 80 mg of doxycycline.DORYX (doxycycline hyclate delayed-release tablets, USP, 100 mg are white, oval scored tablets containing yellow pellets and debossed with “D|1” on one face and plain on the other. Each tablet contains specially coated pellets of doxycycline hyclate equivalent

49、 to 100 mg of doxycycline.DORYX (doxycycline hyclate delayed-release tablets, USP, 150 mg are white, rectangular dual-scored tablets containing yellow pellets and debossed with “D|D|D” on one face and dual-scored on the other. Each tablet contains specially coated pellets of doxycycline hyclate equi

50、valent to 150 mg of doxycycline.DORYX (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

51、 doxycycline.4 CONTRAINDICATIONSThe drug is contraindicated in persons who have shown hypersensitivity to any of the tetracyclines.PRECAUTIONSAND5 WARNINGSDevelopment5.1 ToothThe use of drugs of the tetracycline-class during tooth development (last half of pregnancy, infancy and childhood to the age

52、 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. Doxycycline should not be used in this age g

53、roup, except for anthrax, including inhalational anthrax (post-exposure, unless other drugs are not likely to be effective or are contraindicated.5.2 Clostridium difficile associated diarrheaClostridium difficile associated diarrhea (CDAD has been reported with use of nearly all antibacterial agents

54、, including DORYX Tablets, 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 produc

55、ing 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 antibacterial use. Careful medical history is necessary since CDA

56、D has been reported to occur over two months after the administration of antibacterial agents.If CDAD is suspected or confirmed, ongoing antibacterial use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacteri

57、al treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.5.3 PhotosensitivityPhotosensitivity manifested by an exaggerated sunburn reaction has been observed in some individuals taking tetracyclines. Patients apt to be exposed to direct sunlight or ultraviol

58、et light should be advised that this reaction can occur with tetracycline drugs, and treatment should be discontinued at the first evidence of skin erythema.5.4 SuperinfectionAs with other antibacterial preparations, use of DORYX may result in overgrowth of non-susceptible organisms, including fungi. If superinfecti