DOXYCYCLINE HYCLATE- doxycycline hyclate_capsule, gelatin coated

CLINICAL PHARMACOLOGY
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% per 72 hours in individuals with normal function (creatinine clearance about 75 mL/min). This percentage excretion may fall as low as 1 to 5% per 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 to 22 hours) in individuals with normal and severely impaired renal function. Hemodialysis does not alter serum half-life. Results of animal studies indicate that tetracyclines cross the placenta and are found in fetal tissues. 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. Cross resistance with other tetracyclines is common. Doxycycline has been shown to be active against most isolates of the following microorganisms, both in vitro INDICATIONS AND USAGE Gram-Negative Bacteria Acinetobacter Bartonella bacilliformis Brucella Klebsiella Klebsiella granulomatis Campylobacter fetus Enterobacter aerogenes Escherichia coli Francisella tularensis Haemophilus ducreyi Haemophilus influenzae Neisseria gonorrhoeae Shigella Vibrio cholerae Yersinia pestis Gram-Positive Bacteria Bacillus anthracis 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 Treponema pallidum Treponema pallidum subspecies pertenue Ureaplasma urealyticum Parasites Balantidium coli Entamoeba Plasmodium falciparum* *Doxycycline has been found to be active against the asexual erythrocytic forms of Plasmodium falciparum P. falciparum When available, the clinical microbiology laboratory should provide the results of in vitro Quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (MICs). These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized test method 1,2,4 Quantitative methods that require measurement of zone diameters can also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. The zone size provides an estimate of the susceptibility of bacteria to antimicrobial compounds. The zone size should be determined using a standardized test method. 1,3,4 For anaerobic bacteria, the susceptibility to doxycycline can be determined by a standardized test method 5 Table 1: Susceptibility Test Interpretive Criteria for Doxycycline and Tetracycline Bacteria a Minimal Inhibitory Concentration (mcg/mL) Zone Diameter (mm) Agar Dilution (mcg/mL) S I R S I R S I R Acinetobacter spp. <=4 8 >=16 >=13 10-12 <=9 - - - Tetracycline Anaerobes - - - - - - <=4 8 >=16 Bacillus anthracis b <=1 - - - - - - - - Brucella b <=1 - - - - - - - - Enterobacteriaceae <=4 8 >=16 >=14 11-13 <=10 - - - Franciscella tularensis b <= 4 - - - - - - - - Haemophilus influenzae <=2 4 >=8 >=29 26-28 <=25 - - - Mycoplasma pneumoniae b - - - - - - <=2 - - Nocardiae Actinomyces b Neisseria gonorrhoeae c - - - >=38 31-37 <=30 <=0. 5-1 >=2 Streptococcus pneumoniae <=0. 5 >=1 >=28 25-27 <=24 - - - Vibrio cholerae <=4 8 >=16 - - - - - - Yersinia pestis <=4 8 >=16 - - - - - - Ureaplasma urealyticum - - - - - - <=1 - >=2 a b c Neisseria gonorrhoeae A report of “Susceptible” (S) indicates that antimicrobial drug is likely to inhibit growth of the microorganism if the antimicrobial drug reaches the concentration usually achievable at the site of infection. A report of Intermediate Resistant Standardized susceptibility test procedures require the use of laboratory controls to monitor and ensure the accuracy and precision of supplies and reagents used in the assay, and the techniques of the individuals performing the test 1,2,3,4,5,6,7 Table 2: Acceptable Quality Control Ranges for Susceptibility Testing for Doxycycline and Tetracycline QC Strain Minimal Inhibitory Concentration (mcg/mL) Zone Diameter (mm) Agar Dilution (mcg/mL) Enterococcus faecalis ATCC 29212 2 - 8 - Escherichia coli ATCC 25922 0. 5 - 2 18 - 24 - Eubacteria lentum ATCC 43055 2-16 - - Haemophilus influenzae ATCC 49247 4 - 32 14 - 22 - Neisseria gonorrhoeae ATCC 49226 - 30 - 42 0. 25 - 1 Staphylococcus aureus ATCC 25923 - 23 - 29 - Staphylococcus aureus ATCC 29213 0. 5 - - Streptococcus pneumoniae ATCC 49619 0. 12 25 - 34 - Bacteroides fragilis ATCC 25285 - - 0. 5 Bacteroides thetaiotaomicron ATCC 29741 Mycoplasma pneumoniae ATCC 29342 0. 5 Ureaplasma urealyticum ATCC 33175 - - >=8.
Microbiology
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. Cross resistance with other tetracyclines is common. Doxycycline has been shown to be active against most isolates of the following microorganisms, both in vitro INDICATIONS AND USAGE Gram-Negative Bacteria Acinetobacter Bartonella bacilliformis Brucella Klebsiella Klebsiella granulomatis Campylobacter fetus Enterobacter aerogenes Escherichia coli Francisella tularensis Haemophilus ducreyi Haemophilus influenzae Neisseria gonorrhoeae Shigella Vibrio cholerae Yersinia pestis Gram-Positive Bacteria Bacillus anthracis 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 Treponema pallidum Treponema pallidum subspecies pertenue Ureaplasma urealyticum Parasites Balantidium coli Entamoeba Plasmodium falciparum* *Doxycycline has been found to be active against the asexual erythrocytic forms of Plasmodium falciparum P. falciparum
Dilution techniques
Quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (MICs). These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized test method 1,2,4
Diffusion techniques
Quantitative methods that require measurement of zone diameters can also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. The zone size provides an estimate of the susceptibility of bacteria to antimicrobial compounds. The zone size should be determined using a standardized test method. 1,3,4
ANIMAL PHARMACOLOGY AND ANIMAL TOXICOLOGY
Hyperpigmentation of the thyroid has been produced by members of the tetracycline class in the following species: in rats by oxytetracycline, doxycycline, tetracycline PO 4, 4 Minocycline, tetracycline PO 4, Treatment of various animal species with this class of drugs has also resulted in the induction of thyroid hyperplasia in the following: in rats and dogs (minocycline); in chickens (chlortetracycline); and in rats and mice (oxytetracycline). Adrenal gland hyperplasia has been observed in goats and rats treated with oxytetracycline.

INDICATIONS AND USAGE
To reduce the development of drug-resistant bacteria and maintain effectiveness of Doxycycline Hyclate Capsules, USP and other antibacterial drugs, Doxycycline Hyclate Capsules, USP 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: Rickettsiae Mycoplasma pneumoniae Chlamydia trachomatis Chlamydophila psittaci Chlamydia trachomatis Chlamydia trachomatis Chlamydia trachomatis. Ureaplasma urealyticum Borrelia recurrentis Doxycycline is also indicated for the treatment of infections caused by the following gram-negative microorganisms: Haemophilus ducreyi Yersinia pestis Francisella tularensis Vibrio cholerae. Campylobacter fetus Brucella species Bartonella bacilliformis Klebsiella 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 bacteria, when bacteriologic testing indicates appropriate susceptibility to the drug: Escherichia coli. Enterobacter aerogenes Shigella Acinetobacter Haemophilus influenzae Klebsiella Doxycycline is indicated for treatment of infections caused by the following gram-positive microorganisms when bacteriologic testing indicates appropriate susceptibility to the drug: Streptococcus pneumoniae Bacillus anthracis Bacillus anthracis When penicillin is contraindicated, doxycycline is an alternative drug in the treatment of the following infections: Neisseria gonorrhoeae Treponema pallidum Treponema pallidum pertenue Listeria monocytogenes Fusobacterium fusiforme Actinomyces israelii Clostridium In acute intestinal amebiasis, doxycycline may be a useful adjunct to amebicides. In severe acne, doxycycline may be useful adjunctive therapy. Doxycycline is indicated for the prophylaxis of malaria due to Plasmodium falciparum DOSAGE AND ADMINISTRATION section Information for Patients subsection of the PRECAUTIONS section.
Prophylaxis
Doxycycline is indicated for the prophylaxis of malaria due to Plasmodium falciparum DOSAGE AND ADMINISTRATION section Information for Patients subsection of the PRECAUTIONS section

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 dosage 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. In the management of 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 9see WARNINGS 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. The dose may be administered with food, including milk or carbonated beverage, as required. Uncomplicated urethral, endocervical, or rectal infection in adults caused by Chlamydia trachomatis Nongonococcal urethritis (NGU) caused by C. trachomatis U. urealyticum 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 Acute epididymo-orchitis caused by C. trachomatis For prophylaxis of malaria: For 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 to the adult dose. Prophylaxis should begin 1 to 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. 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.

Due to oral doxycycline’s virtually complete absorption, side effects of 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. Hepatotoxicity has been reported rarely. 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 the drugs in the tetracycline class. Most of these patients took medications immediately before going to bed (See DOSAGE AND ADMINISTRATION Skin: toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, maculopapular and erythematous rashes. 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 Immune: Hypersensitivity reactions including urticaria, angioneurotic edema, anaphylaxis, anaphylactoid purpura, serum sickness, pericarditis, exacerbation of systemic lupus erythematosus, and drug rash with eosinophilia and systemic symptoms (DRESS). Blood: Hemolytic anemia, thrombocytopenia, neutropenia, and eosinophilia have been reported. Other: Bulging fontanels in infants and intracranial hypertension in adults (See WARNINGS When given over prolonged periods, tetracyclines have been reported to produce brown-black microscopic discoloration of the thyroid gland. No abnormalities of thyroid function studies are known to occur. To report SUSPECTED ADVERSE REACTIONS, contact West-Ward Pharmaceuticals Corp. at 1-877-233-2001, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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

Pregnancy
Teratogenic Effects. Pregnancy Category D There are no adequate and well-controlled studies on the use of doxycycline in pregnant women. The vast majority of reported experience with doxycycline during human pregnancy is short-term, first trimester exposure. There are no human data available to assess the effects of long-term therapy of doxycycline in pregnant women, such as that proposed for treatment of anthrax exposure. An expert review of published data on experiences with doxycycline use during pregnancy by TERIS en dash the Teratogen Information System en dash concluded that therapeutic doses during pregnancy are unlikely to pose a substantial teratogenic risk (the quantity and quality of data were assessed as limited to fair), but the data are insufficient to state that there is no risk. 8 9 A small prospective study of 81 pregnancies describes 43 pregnant women treated for 10 days with doxycycline during early first trimester. All mothers reported their exposed infants were normal at 1 year of age. 10
Nonteratogenic Effects
See WARNINGS
Nursing Mothers
Tetracyclines are excreted in human milk; however, the extent of absorption of tetracyclines, including doxycycline, by the breastfed infant is not known. Short-term use by lactating women is not necessarily contraindicated; however, the effects of prolonged exposure to doxycycline in breast milk are unknown. 11 WARNINGS
Pediatric Use
Because of the effects of drugs of the tetracycline-class on tooth development and growth, use doxycycline 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 DOSAGE AND ADMINISTRATION

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. Absorption of tetracyclines is impaired by bismuth subsalicylate. Barbiturates, carbamazepine, and phenytoin decrease the half-life of doxycycline. The concurrent use of tetracycline and Penthrane registered Concurrent use of tetracycline may render oral contraceptives less effective.
Drug/Laboratory Test Interactions
False elevations of urinary catecholamine levels may occur due to interference with the fluorescence test.

Susceptibility Testing Methods
When available, the clinical microbiology laboratory should provide the results of in vitro
Anaerobic Techniques
For anaerobic bacteria, the susceptibility to doxycycline can be determined by a standardized test method 5 Table 1: Susceptibility Test Interpretive Criteria for Doxycycline and Tetracycline Bacteria a Minimal Inhibitory Concentration (mcg/mL) Zone Diameter (mm) Agar Dilution (mcg/mL) S I R S I R S I R Acinetobacter spp. <=4 8 >=16 >=13 10-12 <=9 - - - Tetracycline Anaerobes - - - - - - <=4 8 >=16 Bacillus anthracis b <=1 - - - - - - - - Brucella b <=1 - - - - - - - - Enterobacteriaceae <=4 8 >=16 >=14 11-13 <=10 - - - Franciscella tularensis b <= 4 - - - - - - - - Haemophilus influenzae <=2 4 >=8 >=29 26-28 <=25 - - - Mycoplasma pneumoniae b - - - - - - <=2 - - Nocardiae Actinomyces b Neisseria gonorrhoeae c - - - >=38 31-37 <=30 <=0.25 0.5-1 >=2 Streptococcus pneumoniae <=0.25 0.5 >=1 >=28 25-27 <=24 - - - Vibrio cholerae <=4 8 >=16 - - - - - - Yersinia pestis <=4 8 >=16 - - - - - - Ureaplasma urealyticum - - - - - - <=1 - >=2 a b c Neisseria gonorrhoeae A report of “Susceptible” (S) indicates that antimicrobial drug is likely to inhibit growth of the microorganism if the antimicrobial drug reaches the concentration usually achievable at the site of infection. A report of Intermediate Resistant
Quality Control
Standardized susceptibility test procedures require the use of laboratory controls to monitor and ensure the accuracy and precision of supplies and reagents used in the assay, and the techniques of the individuals performing the test 1,2,3,4,5,6,7 Table 2: Acceptable Quality Control Ranges for Susceptibility Testing for Doxycycline and Tetracycline QC Strain Minimal Inhibitory Concentration (mcg/mL) Zone Diameter (mm) Agar Dilution (mcg/mL) Enterococcus faecalis ATCC 29212 2 - 8 - Escherichia coli ATCC 25922 0.5 - 2 18 - 24 - Eubacteria lentum ATCC 43055 2-16 - - Haemophilus influenzae ATCC 49247 4 - 32 14 - 22 - Neisseria gonorrhoeae ATCC 49226 - 30 - 42 0.25 - 1 Staphylococcus aureus ATCC 25923 - 23 - 29 - Staphylococcus aureus ATCC 29213 0.12 - 0.5 - - Streptococcus pneumoniae ATCC 49619 0.015 - 0.12 25 - 34 - Bacteroides fragilis ATCC 25285 - - 0.12 - 0.5 Bacteroides thetaiotaomicron ATCC 29741 Mycoplasma pneumoniae ATCC 29342 0.06 - 0.5 - 0.06 - 0.5 Ureaplasma urealyticum ATCC 33175 - - >=8
Treatment
Doxycycline is indicated for the treatment of the following infections: Rickettsiae Mycoplasma pneumoniae Chlamydia trachomatis Chlamydophila psittaci Chlamydia trachomatis Chlamydia trachomatis Chlamydia trachomatis. Ureaplasma urealyticum Borrelia recurrentis Doxycycline is also indicated for the treatment of infections caused by the following gram-negative microorganisms: Haemophilus ducreyi Yersinia pestis Francisella tularensis Vibrio cholerae. Campylobacter fetus Brucella species Bartonella bacilliformis Klebsiella 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 bacteria, when bacteriologic testing indicates appropriate susceptibility to the drug: Escherichia coli. Enterobacter aerogenes Shigella Acinetobacter Haemophilus influenzae Klebsiella Doxycycline is indicated for treatment of infections caused by the following gram-positive microorganisms when bacteriologic testing indicates appropriate susceptibility to the drug: Streptococcus pneumoniae Bacillus anthracis Bacillus anthracis When penicillin is contraindicated, doxycycline is an alternative drug in the treatment of the following infections: Neisseria gonorrhoeae Treponema pallidum Treponema pallidum pertenue Listeria monocytogenes Fusobacterium fusiforme Actinomyces israelii Clostridium In acute intestinal amebiasis, doxycycline may be a useful adjunct to amebicides. In severe acne, doxycycline may be useful adjunctive therapy.
WARNINGS
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 it has been observed following repeated short-term courses. Enamel hypoplasia has also been reported. Use doxycycline 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. Clostridium difficile C. difficile C. difficile C. difficile If CDAD is suspected or confirmed, ongoing use of antibacterial drugs not directed against C. difficile C. difficile Intracranial hypertension (IH, pseudotumor cerebri) has been associated with the use of tetracyclines including doxycycline hyclate capsules. Clinical manifestations of IH include headache, blurred vision, diplopia, and vision loss; papilledema can be found on fundoscopy. Women of childbearing age who are overweight or have a history of IH are at greater risk for developing tetracycline associated IH. Concomitant use of isotretinoin and doxycycline hyclate capsules should be avoided because isotretinoin is also known to cause pseudotumor cerebri. Although IH typically resolves after discontinuation of treatment, the possibility for permanent visual loss exists. If visual disturbance occurs during treatment, prompt ophthalmologic evaluation is warranted. Since intracranial pressure can remain elevated for weeks after drug cessation patients should be monitored until they stabilize. All tetracyclines form a stable calcium complex in any bone-forming tissue. A decrease in fibula growth rate has been observed in prematures given oral tetracycline in doses of 25 mg/kg every 6 hours. This reaction was shown to be reversible when the drug was discontinued. 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 also been noted in animals treated early in pregnancy. If any tetracycline is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. 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. 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.
Carcinogenesis,Mutagenesis, Impairment of Fertility
Long-term studies in animals to evaluate carcinogenic potential of doxycycline have not been conducted. However, there has been evidence of oncogenic activity in rats in studies with the related antibacterial drugs, oxytetracycline (adrenal and pituitary tumors), and minocycline (thyroid tumors). Likewise, although mutagenicity studies of doxycycline have not been conducted, positive results in in vitro Doxycycline administered orally at dosage levels as high as 250 mg/kg/day had no apparent effect on the fertility of female rats. Effect on male fertility has not been studied.
Labor and Delivery
The effect of tetracyclines on labor and delivery is unknown.
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.
REFERENCES
1. Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Fourth Informational Supplement 2. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard - Ninth Edition 3. Performance Standards for Antimicrobial Disk Diffusion Susceptibility Tests; Approved Standard en dash Eleventh Edition. 4. Methods for Antimicrobial Dilution and Disk Susceptibility Testing of Infrequently Isolated or Fastidious Bacteria; Approved Guideline en dash Second Edition. 5. Methods for Antimicrobial Susceptibility Testing of Anaerobic Bacteria; Approved Standard - Eighth Edition 6. Susceptibility Testing of Mycobacteria, Nocardiae, and Other Aerobic Actinomycetes; Approved Standardem dashSecond Edition. 7. Methods for Antimicrobial Susceptibility Testing for Human Mycoplasmas; Approved Guideline. 8. Teratogenic Effects of Drugs. A Resource for Clinicians (TERIS). 9. 10. 11. Medications and Mothers’ Milk Manufactured By: West-Ward Pharmaceuticals Corp. Repackaged by: Proficient Rx LP Thousand Oaks, CA 91320 Revised June 2016

Proficient Rx LP

DOXYCYCLINE HYCLATE- doxycycline hyclate_capsule, gelatin coated Product manual source documgent