DORYX® Capsules contain specially coated pellets of doxycycline hyclate for oral administration. Also contains lactose, NF; microcrystalline cellulose, NF; povidone, USP. The capsule shell and/or band contains FD and C blue No. 1; FD and C yellow No. 6; D and C yellow No. 10; gelatin, NF; silicon dioxide; sodium lauryl sulfate, NF; titanium dioxide, USP. Doxycycline is a broad-spectrum antibiotic synthetically derived from oxytetracycline and available as doxycycline hyclate. The chemical designation of this light-yellow crystalline powder is alpha-6-desoxy-5-oxytetra-cycline. Doxycycline has a high degree of lipoid solubility and a low affinity for calcium binding. It is highly stable in normal human serum. Doxycycline will not degrade into an epianhydro form.
Tetracyclines are readily absorbed and are bound to plasma proteins in varying degree. They are concentrated by the liver in the bile and excreted in the urine and feces at high concentrations and in a biologically active form.
Doxycycline is virtually completely absorbed after oral administration. Following a 200 mg dose, normal adult volunteers averaged peak serum levels of 2.6 mcg/mL of doxycycline at 2 hours decreasing to 1.45 mcg/mL at 24 hours. 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 1-5%/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 18-22 hours) in individuals with normal and severly impaired renal function.
Hemodialysis does not alter serum half-life.
Microbiology: Doxycycline is primarily bacteriostatic and is thought to exert its antimicrobial effect by the inhibition of protein synthesis. Doxycycline is active against a wide range of gram-positive and gram-negative organisms. The drugs in the tetracycline class have closely similar antimicrobial spectra and cross resistance among them is common.
Susceptibility Tests: Diffusion Techniques: The use of antibiotic disc susceptibility test methods which measure zone diameter gives an accurate estimation of susceptibility of organisms to DORYX®. One such standard procedure 1 has been recommended for use with discs for testing antimicrobials. Doxycycline 30 mcg discs should be used for the determination of the susceptibility of organisms to doxycycline.
With this type of procedure, a report of "susceptible" from the laboratory indicates that the infecting organism is likely to respond to therapy. A report of "intermediate susceptibility" suggests that the organism would be susceptible if high dosage is used or if the infection is confined to tissue and fluids (e.g., urine) in which high antibiotic levels are obtained. A report of "resistant" indicates that the infecting organism is not likely to respond to therapy. With the doxycycline disc, a zone of 16 mm or greater indicates susceptibility, zone sizes of 12 mm or less indicate resistance, and zone sizes of 13 to 15 mm indicate intermediate susceptibility.
Standardized procedures require the use of laboratory control organisms. The 30 mcg tetracycline disc should give zone diameters between 19 and 28 mm for S. aureus ATCC 25923 and between 18 and 25 mm for E. coli ATCC 25922. The 30 mcg doxycycline disc should give zone diameters between 23 and 29 mm for S. aureus ATCC 25923, and between 18 and 24 mm for E. coli ATCC 25922.
Dilution Techniques: A bacterial isolate may be considered susceptible if the MIC (minimal inhibitory concentration) value for doxycycline is less than 4 mcg/mL.
Organisms are considered resistant if the MIC is greater than 12.5 mcg/mL. MICs greater than 4.0 mcg/mL and less than 12.5 mcg/mL indicate intermediate susceptibility.
As with standard diffusion methods, dilution procedures require the use of laboratory control mechanisms. Standard doxycycline powder should give MIC values in the range of 0.25 mcg/mL and 1.0 mcg/mL for S. aureus ATCC 25923. For E. coli ATCC 25922 the MIC range should be between 1.0 mcg/mL and 4.0 mcg/mL.
Doxycycline is indicated in infections caused by the following microorganisms:
Rickettsiae (Rocky Mountain spotted fever, typhus fever and the typhus group, Q fever, rickettsialpox and tick fevers).
Mycoplasma pneumoniae (PPLO, Eaton' agent)
Agents of psittacosis and ornithosis.
Agents of lymphogranuloma venereum and granuloma inguinale.
The spirochetal agent of relapsing fever ( Borrelia recurrentis ).
The following gram-negative microorganisms:
Haemophilus ducreyi chancroid
Yersinia pestis (formerly Pasteurella pestis )
Francisella tularensis (formerly Pasteurella tularensis )
Vibrio cholerae (formerly Vibrio comma )
Campylobacter fetus (formerly Vibrio fetus )
Brucella species (in conjunction with streptomycin)
Because many strains of the following groups of microorganisms have been shown to be resistant to tetracyclines, 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 drug:
Enterobacter aerogenes (formerly Aerobacter aerogenes )
Mima species and Herellea species
Haemophilus influenzae (respiratory infections)
Klebsiella species (respiratory and urinary infections)
Doxycycline is indicated for treatment of infections caused by the following gram-positive microorganisms when bacteriological testing indicates appropriate susceptibility to the drug:
Up to 44 percent of strains of Streptococcus pyogenes and 74 percent of Streptococcus faecalis have been found to be resistant to tetracycline drugs.
Therefore, tetracyclines should not be used for streptococcal disease unless the organism has been demonstrated to be susceptible.
For upper respiratory infections due to group A beta-hemolytic streptococci, penicillin is the usual drug of choice, including prophylaxis of rheumatic fever.
Staphylococcus aureus (respiratory, skin and soft-tissue infections). Tetracyclines are not the drug of choice in the treatment of any type of staphylococcal infection.
When penicillin is contraindicated, doxycycline is an alternative drug in the treatment of infections due to:
Treponema pallidum and Treponema pertenue (syphilis and yaws)
Fusobacterium fusiforme (Vincent's infection)
In acute intestinal amebiasis, doxycycline may be a useful adjunct to amebicides.
In severe acne, doxycycline may be useful adjunctive therapy.
Doxycycline is indicated in the treatment of trachoma, although the infectious agent is not always eliminated, as judged by immunofluorescence.
Inclusion conjunctivitis may be treated with oral doxycycline alone, or with a combination of topical agents.
Doxycycline is indicated for the treatment of uncomplicated urethral, endocervical or rectal infections in adults caused by Chlamydia trachomatis. 2
Doxycycline is indicated for the treatment of nongonococcal urethritis caused by Chlamydia trachomatis and Ureaplasma urealyticum and for the treatment of acute epididymo-orchitis caused by Chlamydia trachomatis. 2
Doxycycline is indicated for the treatment of uncomplicated gonococcal infections in adults (except for anorectal infections in men), the gonococcal arthritis-dermatitis syndrome and acute epididymo-orchitis caused by N. gonorrhoeae. 2
The drug is contraindicated in persons who have shown hypersensitivity to any of the tetracyclines.
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). This adverse reaction is more common during long term use of the drugs but has been observed following repeated short term courses. Enamel hypoplasia has also been reported. TETRACYCLINE DRUGS, THEREFORE, SHOULD NOT BE USED IN THIS AGE GROUP UNLESS OTHER DRUGS ARE NOT LIKELY TO BE EFFECTIVE OR ARE CONTRAINDICATED.
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 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 potential hazard to the fetus.
As with other tetracyclines, doxycycline forms 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.
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.
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.
As with other antibiotic preparations, use of this drug may result in overgrowth of nonsusceptible organisms, including fungi. If superinfection occurs, the antibiotic should be discontinued and appropriate therapy instituted.
All infections due to group A beta-hemolytic streptococci should be treated for at least 10 days.
Laboratory tests: In venereal disease when coexistent syphilis is suspected, dark-field examination should be done before treatment is started and the blood serology repeated monthly for at least 4 months.
In long term therapy, periodic laboratory evaluation 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.
For concomitant therapy with antacids or iron-containing preparations and food see DOSAGE AND ADMINISTRATION section.
Carcinogenesis, mutagenesis, impairment of fertility: Long-term studies are currently being conducted to determine whether tetracyclines have carcinogenic potential. Animal studies conducted in rats and mice have not provided conclusive evidence that tetracyclines may be carcinogenic or that they impair fertility. In two mammalian cell assays (L51784 mouse lymphoma and Chinese hamster lung cells in vitro ), positive responses for mutagenicity occurred at concentrations of 60 and 10 mcg/mL, respectively. In humans, no association between tetracyclines and these effects have been made.
Pregnancy Pregnancy Category D (see section).
Nursing mothers: Tetracyclines are present in the milk of lactating women who are taking a drug in this class. Because of the potential for serious adverse reactions in nursing infants from the tetracyclines, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother (see section).
Pediatric use: See and DOSAGE AND ADMINISTRATION sections.
Due to oral doxycycline' 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. 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 section).
Skin: Maculopapular and erythematous rashes. Exfoliative dermatitis has been reported but is uncommon. Photosensitivity is discussed above (see section).
Renal toxicity: Rise in BUN has been reported and is apparently dose-related (see section).
Hypersensitivity reactions: Urticaria, angioneurotic edema, anaphylaxis, anaphylactoid purpura, pericarditis, and exacerbation of systemic lupus erythematosus.
Bulging fontenals in infants and benign intracranial hypertension in adults have been reported in individuals receiving tetracyclines. These conditions disappeared when the drug was discontinued.
Blood: Hemolytic anemia, thrombocytopenia, neutropenia, and eosinophilia have been reported with tetracyclines.
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.
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) 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.
For pediatric patients above eight years of age: The recommended dosage schedule for pediatric patients weighing 100 pounds or less is 2 mg/lb of body weight divided into two doses on the first day of treatment, followed by 1 mg/lb of body weight given as a single daily dose or divided into two doses on subsequent days. For more severe infections up to 2 mg/lb of body weight may be used. For pediatric patients over 100 pounds, the usual adult dose should be used.
Uncomplicated gonococcal infections in adults (except anorectal infections in men): 100 mg, by mouth, twice-a-day for 7 days. 2 As an alternate single visit dose, administer 300 mg stat followed in one hour by a second 300 mg dose. The dose may be administered with food, including milk or carbonated beverage, as required.
Acute epididymo-orchitis caused by N. gonorrhoeae: 100 mg, by mouth, twice-a-day for at least 10 days. 2
Primary and secondary syphilis: 300 mg a day in divided doses for at least 10 days. 2
Uncomplicated urethral, endocervical, or rectal infection in adults caused by Chlamydia trachomatis: 100 mg by mouth, twice-a-day for at least 7 days. 2
Nongonococcal urethritis caused by C. trachomatis and U. urealyticum: 100 mg, by mouth, twice-a-day for at least 7 days. 2
Acute epididymo-orchitis caused by C, trachomatis: 100 mg, by mouth, twice-a-day for at least 10 days. 2
The therapeutic antibacterial serum activity will usually persist for 24 hours following recommended dosage.
When used in streptococccal 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 section).
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.
Concomitant therapy: Antacids containing aluminum, calcium or magnesium, sodium bicarbonate, and iron-containing preparations should not be given to patients taking oral tetracyclines.
Studies to date have indicated that administration of doxycycline at the usual recommended doses does not lead to excessive accumulation of the antibiotic in patients with renal impairment.
DORYX® Capsules have a yellow transparent body with light blue opaque cap; the capsule bearing the inscription "DORYX" in white. Pellets are colored yellow. Each capsule contains specially coated pellets of doxycycline hyclate equivalent to 100 mg of doxycycline, supplied in:
Bottles of 50 capsules ................. N 0430-0838-19
Store at controlled room temperature below 25°C (77°F).
Revised December 1999
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