text:
Label: DOXYCYCLINE HYCLATE tablet, film coated
- NDC Code(s): 42806-312-01, 42806-312-05, 42806-312-50
- Packager: Epic Pharma, LLC
- Category: HUMAN PRESCRIPTION DRUG LABEL
Drug Label Information
Updated November 8, 2021
If you are a healthcare professional or from the pharmaceutical industry please visit this version.
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- Official Label (Printer Friendly)
Doxycycline is an antibacterial drug synthetically derived from oxytetracycline, and is available as doxycycline hyclate tablets for oral administration. The chemical designation of doxycycline is 4-(Dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-2-naphthacene-carboxamide monohydrochloride, compound with ethyl alcohol (2:1), monohydrate.
The structural formula of doxycycline hyclate is:
with a molecular formula of (C22H24N2O8•HCl)2•C2H6O•H2O and the molecular weight is 1025.89. Doxycycline is a light-yellow crystalline powder. Doxycycline hyclate is soluble in water.
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.
Active Ingredient: Doxycycline hyclate USP equivalent to 100 mg of doxycycline.
Inactive Ingredient: Microcrystalline cellulose and magnesium stearate.
Tablet coating contains hypromellose, titanium dioxide, polyethylene glycol, FD&C yellow #6, polysorbate 80 and FD&C blue #2.
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 to 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 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.
Population pharmacokinetic analysis of sparse concentration-time data of doxycycline following standard of care intravenous and oral dosing in 44 pediatric patients (2 to 18 years of age) showed that allometrically -scaled clearance (CL) of doxycycline in pediatric patients ≥2 to ≤8 years of age (median [range] 3.58 [2.27 to 10.82] L/h/70 kg, N =11) did not differ significantly from pediatric patients >8 to 18 years of age (3 .27 [1.11 to 8.12] L/h/70 kg, N=33). For pediatric patients weighing ≤45 kg, body weight normalized doxycycline CL in those ≥2 to ≤8 years of age (median [range] 0.071 [0 .041 to 0.202] L/kg/h, N=10) did not differ significantly from those >8 to 18 years of age (0.081 [0.035 to 0.126] L/kg/h, N=8). In pediatric patients weighing >45 kg, no clinically significant differences in body weight normalized doxycycline CL were observed between those ≥2 to ≤8 years (0.050 L/kg/h, N=l) and those >8 to 18 years of age (0.044 [0.014 to 0.121] L/kg/h, N=25). No clinically significant difference in CL between oral and IV dosing was observed in the small cohort of pediatric patients who received the oral (N=19) or IV (N=21) formulation alone.
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.
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.
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
To reduce the development of drug-resistant bacteria and maintain effectiveness of doxycycline hyclate and other antibacterial drugs, doxycycline hyclate 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 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 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.
Doxycycline is indicated for the prophylaxis of malaria due to Plasmodium falciparum in short-term travelers (<4 months) to areas with chloroquine and/or pyrimethamine-sulfadoxine resistant strains. (See DOSAGE AND ADMINISTRATION section and Information for Patients subsection of the PRECAUTIONS section.)
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 associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including doxycycline hyclate 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 producing 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 the use of antibacterial drugs. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.
If CDAD is suspected or confirmed, ongoing use of antibacterial drugs not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.
Severe skin reactions, such as exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported in patients receiving doxycycline. (See ADVERSE REACTIONS.) If severe skin reactions occur, doxycycline should be discontinued immediately, and appropriate therapy should be instituted.
Intracranial hypertension (IH, pseudotumor cerebri) has been associated with the use of tetracyclines including doxycycline. 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 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. 0Since 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.
As with other antibacterial drugs, use of doxycycline hyclate tablets may result in overgrowth of nonsusceptible organisms, including fungi. If superinfection occurs, doxycycline hyclate tablets should be discontinued and appropriate therapy instituted.
Incision and drainage or other surgical procedures should be performed in conjunction with antibacterial therapy, when indicated.
Doxycycline offers substantial but not complete suppression of the asexual blood stages of Plasmodium strains.
Doxycycline does not suppress P. falciparum's sexual blood stage gametocytes. Subjects completing this prophylactic regimen may still transmit the infection to mosquitoes outside endemic areas.
Prescribing doxycycline hyclate tablets in the absence of proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
Information for Patients
Patients taking doxycycline for malaria prophylaxis should be advised:
- •
- that no present-day antimalarial agent, including doxycycline, guarantees protection against malaria.
- •
- to avoid being bitten by mosquitoes by using personal protective measures that help avoid contact with mosquitoes, especially from dusk to dawn (e.g., staying in well-screened areas, using mosquito nets, covering the body with clothing, and using an effective insect repellent).
- •
- that doxycycline prophylaxis:
- •
- should begin 1to 2 days before travel to the malarious area,
- •
- should be continued daily while in the malarious area and after leaving the malarious area,
- •
- should be continued for 4 further weeks to avoid development of malaria after returning from an endemic area,
- •
- should not exceed 4 months.
All patients taking doxycycline should be advised:
- •
- to avoid excessive sunlight or artificial ultraviolet light while receiving doxycycline and to discontinue therapy if phototoxicity (e.g., skin eruption, etc.) occurs. Sunscreen or sunblock should be considered. (See WARNINGS.)
- •
- to drink fluids liberally along with doxycycline to reduce the risk of esophageal irritation and ulceration. (See ADVERSE REACTIONS.)
- •
- that the absorption of tetracyclines is reduced when taken with foods, especially those which contain calcium. However, the absorption of doxycycline is not markedly influenced by simultaneous ingestion of food or milk. (See DRUG INTERACTIONS.)
- •
- that the absorption of tetracyclines is reduced when taking bismuth subsalicylate. (See DRUG INTERACTIONS.)
- •
- that the use of doxycycline might increase the incidence of vaginal candidiasis.
Patients should be counseled that antibacterial drugs, including doxycycline hyclate tablets should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When doxycycline hyclate tablets are prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses ornot completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by doxycycline hyclate tablets or other antibacterial drugs in the future.
Diarrhea is a common problem caused by antibacterial drugs, which usually ends when the antibacterials are discontinued. Sometimes after starting treatment with antibacterial drugs, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibacterial drug. If this occurs, patients should contact their physician as soon as possible.
Laboratory Tests
In venereal disease, when co-existent syphilis is suspected, dark field examinations 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.
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® (methoxyflurane) has been reported to result in fatal renal toxicity.
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.
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 mammalian cell assays have been reported for related antibacterial drugs (tetracycline, oxytetracycline).
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.
Pregnancy: Teratogenic Effects.
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 – the Teratogen Information System – 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 risk1. A case-control study (18,515 mothers of infants with congenital anomalies and 32,804 mothers of infants with no congenital anomalies) shows a weak but marginally statistically significant association with total malformations and use of doxycycline anytime during pregnancy. Sixty-three (0.19%) of the controls and fifty-six (0.30%) of the cases were treated with doxycycline. This association was not seen when the analysis was confined to maternal treatment during the period of organogenesis (i.e., in the second and third months of gestation) with the exception of a marginal relationship with neural tube defect based on only two exposed cases2.
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 age3.
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 unknown4. Because of the potential for serious adverse reactions in nursing infants from doxycycline, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. (See 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 and DOSAGE ANDADMINISTRATION.)
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, inflammatory lesions (with monilial overgrowth) in the anogenital region, and pancreatitis. Hepatotoxicity has been reported rarely. 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.) 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 reaction 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 Epic Pharma at 1-888-374-2791, or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
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.
The usual dose of oral 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/day.
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. 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: 100 mg, by mouth twice a day for 7 days.
Nongonococcal urethritis (NGU) caused by C. trachomatis or 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.
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 hyclate tablets, 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.
Doxycycline hyclate tablets, USP equivalent to 100 mg of doxycycline: Beige color, round convex, film coated tablets debossed "312" below, "B" on one side and plain on the other.
Bottles of 50 tablets NDC 42806-312-50
Bottles of 100 tablets NDC 42806-312-01
Bottles of 500 tablets NDC 42806-312-05
Store at 20° to 25°C (68° to 77°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.
Hyperpigmentation of the thyroid has been produced by members of the tetracycline class in the following species: in rats by oxytetracycline, doxycycline, tetracycline PO4, and methacycline; in minipigs by doxycycline, minocycline, tetracycline PO4, and methacycline; in dogs by doxycycline and minocycline; in monkeys by minocycline.
Minocycline, tetracycline PO4, methacycline, doxycycline, tetracycline base, oxytetracycline HCl, and tetracycline HCl were goitrogenic in rats fed a low iodine diet. This goitrogenic effect was accompanied by high radioactive iodine uptake. Administration of minocycline also produced a large goiter with high radioiodine uptake in rats fed a relatively high iodine diet.
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.
- Friedman JM and Polifka JE. Teratogenic Effects of Drugs. A Resource for Clinicians (TERIS). Baltimore, MD: The Johns Hopkins University Press, 2000: 149–195.
- Cziezel AE and Rockenbauer M. Teratogenic study of doxycycline. Obstet Gynecol 1997; 89: 524–528.
- Horne HW Jr and Kundsin RB. The role of mycoplasma among 81 consecutive pregnancies: a prospective study. Int J Fertil 1980; 25: 315–317.
- Hale T. Medications and Mothers Milk. 9th edition. Amarillo, TX: Pharmasoft Publishing, 2000: 225–226.
Distributed by:
Epic Pharma, LLC
Laurelton, NY 11413 USA
Product of USA
- PACKAGE/LABEL PRINCIPAL DISPLAY PANEL – 100 mg, 50 Tablets
doxycycline hyclate tablet, film coatedProduct Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:42806-312 Route of Administration ORAL Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength DOXYCYCLINE HYCLATE (UNII: 19XTS3T51U) (DOXYCYCLINE ANHYDROUS - UNII:334895S862) DOXYCYCLINE ANHYDROUS 100 mg Inactive Ingredients Ingredient Name Strength MICROCRYSTALLINE CELLULOSE (UNII: OP1R32D61U) MAGNESIUM STEARATE (UNII: 70097M6I30) HYPROMELLOSE, UNSPECIFIED (UNII: 3NXW29V3WO) POLYETHYLENE GLYCOL, UNSPECIFIED (UNII: 3WJQ0SDW1A) TITANIUM DIOXIDE (UNII: 15FIX9V2JP) FD&C YELLOW NO. 6 (UNII: H77VEI93A8) POLYSORBATE 80 (UNII: 6OZP39ZG8H) FD&C BLUE NO. 2 (UNII: L06K8R7DQK) Product Characteristics Color BROWN (BEIGE) Score no score Shape ROUND (convex) Size 9mm Flavor Imprint Code 312;B Contains Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:42806-312-50 50 in 1 BOTTLE; Type 0: Not a Combination Product 10/01/2016 2 NDC:42806-312-01 100 in 1 BOTTLE; Type 0: Not a Combination Product 10/01/2016 3 NDC:42806-312-05 500 in 1 BOTTLE; Type 0: Not a Combination Product 10/01/2016 Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA062269 10/01/2016 Labeler - Epic Pharma, LLC (827915443) Registrant - Caribe Holdings (Cayman) Co. Ltd. dba PuraCap Caribe (080230346) Establishment Name Address ID/FEI Business Operations Caribe Holdings (Cayman) Co. Ltd. dba PuraCap Caribe 080230346 MANUFACTURE(42806-312)


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text:
Of the last 13 puzzles, ubragg has taken 8 and Mr C the other 5.
The solution to yesterday's puzzle reads "MEET ME OCTOBER 27 AT 10PM AT THE BAR IN THE SCANDIC SOLSIDEN HOTEL".
The maze is a huge Rubik's Cube. Each room is one of the 27 cells of the cube, and each has at least one and up to three of its walls colored (except the "Dark Room") representing the colored sides on the exterior of the cube. Note that a Rubik's Cube has 6 sides, 27 smaller cubes (rooms), 54 smaller square-shaped exterior surfaces, and 162 total cell surfaces (interior and exterior). Each of these different types of entities will come into play. Also note this puzzle was a major pain in the butt to make.
The first step is to wander through the rooms and record your observations. Namely, the locations of the colored walls, any letters etched in the walls, the words that burn in the fires, and any doors.
If done correctly one can determine the initial state of the cube:
Here's another representation of the cube's initial state, unfolded into 2-D form to show all 6 sides/54 exterior cell surfaces:
And here's a mapping of each room's doors and locator ID's (which are the post titles, which though irrelevant to the puzzle solution can help track the rooms):
The center cell is the "Dark Room," which is dark because there is no exterior surface. It's also the only one of the 27 cells that does not move when the cube is twisted. The poem in the Dark Room tells you you must solve the Cube in 3 twists. Using the I,II,III; 1,2,3; and a,b,c conventions above, those 3 moves are:
- Twist top layer I to the right
- Twist East layer c downward
- Twist bottom layer III to the left
The Dark Room poem further hints that you must read three exterior surfaces before each of your three moves:
- Before the 1st twist, read the floor
- Before the 2nd twist, read the South wall
- Before the 3rd and final twist, read the East wall
- And after the 3rd twist, when the cube is solved, read the words in the fire.
Focusing first on the 1st three twists, the relevant surfaces read as follows:
A clear message is emerging: "MEET ME OCTOBER 27 AT 10PM AT THE B..."
Finally, to complete the message as per step 4, you must take the final state of the puzzle and read first letter of each of the words in the firewood and read them as indicated in the poem:
Put it all together to get the full message:
The Scandic Solsiden Hotel! - 30 minutes from Trondheim airport, and a short walk from Pirbadet, Nidaros Cathedral, and Stiftsgaarden wooden palace. Make your reservation here!
And finally, on the off-chance anyone is interested, here's the overall key I used to track each rooms' fire-words, doors, and surfaces:
Congratulations to UBragg, QuadSevens, Mr C, and Jason. Well done to all!
Coming tomorrow: Look inside the mind of Quad, Mr C, and Jason (they have one each), as they have each submitted their puzzle-mapping worksheets. Anyone else who has one, successful or not, please submit and I'll publish (Mr F - I know you have one, let's see it! UBragg - I'm not sure if you have one, as you may have done it in your head, but if you do, please submit as well)
Thanks everyone for another fun puzzle season, hope you enjoyed. Final Rankings to post soon!


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There are certain topics that even some of the smartest people I talk with who aren't startup oriented can't fully grok. One of them is whether profitability matters. It's common cocktail party chatter to hear people confidently pronounce that some well known startup is sure to blow up.
Or you know the other one — the one where Snapchat lost $2 billion in just one quarter. Two-fucking-billion! What a disaster! Except that they didn't actually lose $2 billion in cash. It was a stock option incentive related "expense" but I bet you didn't know that because in an era where we only read the headlines — they must be a train wreck losing billions. (They actually lost about $175 million in cash in that quarter, FWIW. See appendix if you want to know more on this.)
"How could they succeed when they're not even profitable!"
If you hire 6 senior sales reps in January at $120,000 / year salary then you've taken on an extra $60,000 per month in costs yet these sales people might not close new business for 6 months. Your profitability will go down for 2 quarters while your growth may increase dramatically in quarters 3–12.
I know this seems obvious but I promise you that even smart people forget this when talking about profitability. 70–80% of the costs of most startups are employee costs so what you're really talking about when a company is unprofitable is that they are growing their staff ahead of their revenue.


text:
This post was last updated at 4:40 p.m. ET.
The victims of the Navy Yard shootings that brought panic and tragedy to a corner of Washington, D.C., on Monday morning are in many people's thoughts as their names and other information are released. We'll collect what we know about the victims here.
The identities of the 13 people, including the gunman, who died and at least eight who were wounded are being released by officials as family members are informed of the victims' statuses. Police have now identified all of those who died in Monday's violence, including the alleged gunman, Aaron Alexis, 34.
Update at 12:30 p.m. ET: Complete List Of Those Killed
Shortly after noon Tuesday, Washington's Metropolitan Police Department issued the names of five victims who died in the attack and were not named in Monday night's news conference. We've updated our list below and will be adding more details about their lives as we learn them.
Our original post continues:
On Tuesday morning, Defense Secretary Chuck Hagel and other officials held a wreath-laying ceremony at the U.S. Navy Memorial plaza to honor the victims of the attack, which occurred at around 8:20 a.m. in Building 197 of the Navy Yard, a popular morning spot with a breakfast cafeteria.
Several of those who were hurt or killed Monday had worked at the Navy Yard for decades. As of Tuesday afternoon, all 12 victims who died in the attack had been identified:
Michael Arnold, 59, of Lorton, Va., was a "wonderful person and a wonderful neighbor," a neighbor told The Washington Post. The woman was on her way to visit Arnold's wife.
A retired Navy officer who was working as a consultant on ship design, Arnold was also a pilot who was building his own airplane, his uncle, Steve Hunter, told The Associated Press in an interview from Rochester, Mich., where Arnold grew up.
"Arnold and his wife, Jolanda, had been married for more than 30 years," the AP reports, citing Hunter. "They had two grown sons, Eric and Christopher."
Martin Bodrog, 54, was a Navy veteran who lived in Annandale, Va. He is listed in a LinkedIn account as a senior analyst at T-MB — the Tech-Marine Business.
The company's staff includes many former military officers, according to its website. A listing of recent work includes service and support contracts with elements of the U.S. Navy, with several having a presence at the Navy Yard.
Bodrog "had been married to his wife, Melanie, for 25 years," ABC reports. "The couple had three daughters, Isabel, 23, Sophie, 17, and Rita, 16."
He was a thoughtful neighbor who "taught Sunday school and was a die-hard Boston Bruins fan," says ABC, which received a copy of Bodrog's obituary.
Arthur Daniels, 51, of southeast Washington, D.C., saw the attack unfold Monday and attempted to get to safety, according to a witness. But he was shot in the back after waiting for an elevator door to open, reports The Post, citing a man who worked with Daniels.
Daniels had worked as a subcontractor, moving and installing furniture in government buildings; his job took him to the Navy Yard on Monday, The Post says, citing an interview with family members and others. The newspaper says Daniels had five children and nine grandchildren.
"I don't know why they shot him," Priscilla Daniels said of her husband. "He was a good father and hard worker."
Sylvia Frasier, 53, of Charles County, Md., worked in computer network security at the Naval Sea Systems Command. Word of her fate didn't reach some family members until just before 10 last night, The Post says.
Frasier's family, including her six siblings, tell the newspaper that they had been told earlier Monday that Sylvia had been hurt and was in the hospital. But they prepared themselves for the worst.
"No matter how we feel, no matter what information we get from the FBI, we have got to forgive," her sister Wendy Edmonds, 52, told other family members before they received the sad news. "We have to forgive. We can't become bitter."
Kathy Gaarde, 62, of Woodbridge, Va., was a financial analyst who a neighbor says may have been close to retiring; her husband retired from the Navy last year, the AP reports.
"Today my life partner of 42 years (38 of them married) was taken from me, my grown son and daughter, and friends," her husband, Douglass Gaarde, wrote in an email to the news agency. "We were just starting to plan our retirement activities and now none of that matters. It hasn't fully sunk in yet but I know I already dearly miss her."
A neighbor, Patrick Bolton, tells The Post that Gaarde "was just the kindest lady in the world." He added, "I'm not even exaggerating. I've never seen her do anything but nice things for people."
John Roger Johnson, 73, was a longtime resident of Derwood, Md., who loved kids, a neighbor tells The Post.
A friend and former co-worker, William Venable, tells NPR's Hansi Lo Wang that Johnson, or J.J., was his colleague in the IT department, doing things like distributing cellphones and wireless cards. The job could be tedious — but every day, Venable says, Johnson greeted him with the same enthusiasm.
"His greeting to me — every day, religiously — was, 'How ya doin' buddy?!' "
"I'm a 20-something-year-old black man, and he's a 70-plus-year-old white guy," Venable says. "You know, we had zero in common. But we had great conversations, and he was a great spirit; it was a spirit that you could connect with. He was one of my best friends in that place."
Frank Kohler, 50, of St. Mary's County, Md., also died in Monday's attack. He lived in Tall Timbers, where his two daughters graduated from Kings Christian Academy, reports The Baynet.com.
This afternoon, the news site reported that Kohler's neighbor, Merl Evans, "said the family had a tough time of it in recent years, including their house burning down in a gas explosion. They lost everything, but rebuilt, Evans said."
Kohler is described as having been active in the Rotary Club, "and will be especially missed at the organization's upcoming St. Mary's County Oyster Festival. He was president of the organization in 2005 and was the festival's King Oyster the following year."
The Baynet.com says that Kohler was an engineer who previously worked for Lockheed Martin; his purpose at the Navy Yard Monday has not been reported.
Mary Francis Knight, 51, of Reston, Va., was a deputy chief information officer at Naval Sea Systems Command who specialized in cybersecurity, according to a LinkedIn profile under her name.
She also taught at Northern Virginia Community College, where a spokeswoman tells ABC News that Knight was slated to teach computer courses this fall.
Vishnu Pandit, 61, had lived in North Potomac, Md., for at least 20 years, The Post reports. A neighbor tells the newspaper they saw many cars arrive at the Pandit family's house late Monday. Another neighbor, Mike Honig, described Pandit as "a very nice man with an Irish setter."
After immigrating to the United States from India in the 1970s, Pandit obtained degrees in marine engineering, according to Huffington Post.
The site spoke to M. Nuns Jain, a colleague of Pandit's who was at the family's home this week.
"He definitely lived the American Dream and achieved it," Jain said. "It's disheartening that the one flaw in the American system is the uncontrollable proliferation of guns."
Kenneth Bernard Proctor, 46, Waldorf, Md., was a civilian utilities foreman who had worked for the government for 22 years, his ex-wife, Evelyn Proctor, tells the AP. He was, she says, "a very loving, caring, gentle person. His kids cfmeant a lot to him."
The couple have two teenage sons — one is 15; the other is in basic training after enlisting in the Army.
Evelyn Proctor says her ex-husband didn't work in Building 197, but had gone there for his usual breakfast. She said they had talked on the phone Monday morning, and she learned of his death Monday evening.
"We were still very close. It wasn't a bitter divorce," she said. The pair had dated as far back as high school. "We still talked every day, and we lived 10 minutes away from each other."
Gerald L. Read, 58, of Alexandria, Va., had worked as an information assurance specialist at Naval Sea Systems Command in the Navy Yard, a post he held for the past 12 years, according to a LinkedIn account in his name.
Richard Michael Ridgell, 52, of Westminster, Md., was a father who worked as a security guard at the Navy Yard, according to the Carroll County Times.
A retired Maryland state trooper, Ridgell helped coach a Jaycees Girls Softball team. According to the newspaper, Ridgell's daughters played for the team.
"Mike was the kind of guy that you would want your daughter to be coached by," says Tom Whitcomb, a coach for the team who knew Ridgell for about 10 years. "He was always positive. He was always encouraging."
Of at least eight people who were wounded Monday, three were shot and the rest reportedly suffered other injuries.
Police officer Scott Williams underwent surgery after suffering gunshot wounds to his legs. D.C. officials said he is recovering and talkative. At a news conference Monday night, Metropolitan Police Chief Cathy Lanier said she and Williams entered the police force around the same time, and that he has "a stellar record."
And it seems that Mr. Williams is also a man with priorities.
"The police officer when he came in ... he was most concerned about being able to talk to his mother," Dr. Janis Orlowski, chief medical officer at Washington Hospital Center, tells NPR member station WAMU. Williams "wanted to make sure that he was able to speak to her before he went into surgery. You know ... you always have to take care of Mom," she said.
Williams and two civilians, both women, were all able to talk with medical and police staff and are expected to recover, Orlowski says. One of the women had surgery for a wound to her shoulder; the other did not need surgery, despite a wound to her head.
"She's a very, very lucky young lady," Orlowski says. "She had an injury to her hand and her head. But the bullet did not actually penetrate the skull. It did not penetrate the bone."
The Navy says it is providing counseling and other services to employees and family members at Joint Base Anacostia-Bowling. The service asks those who need help or information to call 1-855-677-1755. People can also call 1-800-222-0364 for counseling, the Navy says.
Copyright 2021 NPR. To see more, visit https://www.npr.org.


text:
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Facebook CEO Mark Zuckerberg gave his first public interview after his tech company's rocky IPO and the disappointing stock performance that followed. Facebook's share price is now worth about $19 — half as much as it was priced back in May when its stock first went on the market.
Zuckerberg took questions from Michael Arrington at TechCrunch Disrupt, a San Francisco conference for startups. We watched and listened in to the talk in case you missed it:
Building a mission and business go hand-in-hand
When asked whether Facebook has a morale problem with the stock-price fluctuations, Zuckerberg said the price "doesn't help." But the CEO said this isn't the company's first up-and-down season.
"People at Facebook are used to the press saying good and bad things," he said. What motivates Facebook employees "is building stuff that they're proud of. This isn't just Facebook. This is universal ... It's a great time for people to stay and double down."
Going forward, it's all about mobile
"Now we really are a mobile company. All the code we write is [for] mobile," Zuckerberg said.
He even acknowledged writing his founder's letter to current and potential shareholderson his mobile phone.
"I do everything on my phone," he said. "A lot of people do."
The decision to move to a mobile-first strategy follows that of most technology companies, which note that mobile platforms are where users are spending more time.
"On engagement, we're already seeing that mobile users are more likely to be daily active users than desktop users," Zuckerberg said. "They're more likely to use Facebook six or seven days of the week."
Mobile platforms also present new and different opportunities for making money.
Profiting on mobile is more akin to how TV makes money
Ads have to be more integrated on mobile because, unlike on a screen, there's no right rail on which to put ads. Zuckerberg says Facebook's product teams are thinking about developing new features with advertising fundamentally integrated.
"I think we know that we're going to do well on that," he said. "The question is getting there."
Going all in on HTML5 was a major misstep
When it came to developing Facebook for various platforms, the company's decision to code in HTML5 was its biggest mistake, Zuckerberg said, costing it two years and ultimately not panning out.
"We were just never able to get the quality we wanted," he said.
After failing in its effort, the Facebook team had to start over and rewrite its applications code in "native."
Native applications are built using device-specific tools, which require specialized coding skills and have to be written for each platform. But the upside is they can do fancier things and are often faster.
"The apps are now going to be in better shape now," Zuckerberg said.
Workflow inside Facebook changed
In a part of the talk that will appeal to you systems and workflow techies out there, Zuckerberg explained that the company went from being functionally organized — with one head of engineering, one head of product — to product groups. Today, Facebook has a newsfeed group, a platform product group, etc.
"Now there's a person who owns each one of those," he said.
Zuckerberg said this organizational structure will lead to some exciting rollouts in six to nine months.
On Instagram: 'They're killing it'
Facebook bought photo-sharing site Instagram for a cool $1 billion this summer (though the value of the deal has fallen along with Facebook's stock), a move that led to mixed reviews for both companies involved in the deal.
But Zuckerberg says it was a marriage that benefited both sides. He explained that Instagram was starting to get a lot of distribution on Facebook, but didn't want to bet just on one company; Facebook, on the other hand, didn't want to help Instagram with an abundance of resources without gaining value.
So, eventually Zuckerberg decided they could just become one company.
"We're going to execute on the features we decided on early," he said. "We want to help it grow to hundreds of millions of users. But we have no agenda of making them go onto our infrastructure. ... I think it's primarily a waste of time."
Facebook is not making a Facebook phone
"It's so clearly the wrong strategy for us," Zuckerberg said.
He argued that if Facebook theoretically built a phone, it wouldn't move the needle for the social-networking company. The Facebook strategy he outlined is distinct from other tech companies that are getting into hardware. It's to build a system that's integrated into every major device people want to use, instead of building the devices themselves.
Search is an "obvious thing" Facebook would want to do in the future
Facebook's search feature already gets a billion queries a day without trying, Zuckerberg said.
"Most of it is people trying to find people, but others are people looking for brand pages or apps that links to commercial behavior," he said. "I think there's a big opportunity there."
He observed that the nature of search engines is evolving to give users a set of answers instead of merely a collection of relevant information.
"Facebook is uniquely positioned to answer questions that people have, like, what sushi restaurants have my friends gone to in New York lately and liked? ... These are queries you could potentially do with Facebook that you couldn't do with anything else, we just have to do it," he said.
Zuckerberg says there is a search team at Facebook, but won't say how many engineers are on the team.
For Zuckerberg, it's not about fun, it's about mission
With his anxious and speedy delivery on stage, it was unclear whether Zuckerberg was enjoying himself at all these days. But he said that's not the point.
"There are times when everyone in the world thinks what we're doing is awesome. ... There are times when people are superpessimisitic," he said. "I personally would rather be in the cycle when people underestimate us. I think it gives us latitude to go out and take some big bets and do some things that excite and amaze people."
He wants the legacy to be connecting to everyone in the world.
Zuckerberg only codes for fun now
Zuckerberg says he doesn't code to the main branch of Facebook anymore because he doesn't want anyone else to have to keep up with what he does.
"Everything I [do] ... breaks," he said of his programming.
He talks really fast
Copyright 2016 NPR. To see more, visit http://www.npr.org/.


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We share the same goal – ensuring your animal companion is healthy and happy!
Google has made it easy and fast to find health-related information. Although much of it is valuable, sometimes it may be inaccurate or out of date. You need properly documented and approved information to make the best choice for your pet.
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Please feel free to browse our library of topics or quickly find the article you need by using our easy-to-use search system.


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If you own a business, you probably own some form of general liability insurance to protect you in the event of a lawsuit due to negligence on your part. However, there may be situations where the limits of your general policy may not provide adequate protection. A commercial umbrella can provide you and your business with additional liability protection.
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King James Version
2Chronicles 32
1 After these things, and the establishment thereof, Sennacherib king of Assyria came, and entered into Judah, and encamped against the fenced cities, and thought to win them for himself.
2 And when Hezekiah saw that Sennacherib was come, and that he was purposed to fight against Jerusalem,
3 He took counsel with his princes and his mighty men to stop the waters of the fountains which were without the city: and they did help him.
4 So there was gathered much people together, who stopped all the fountains, and the brook that ran through the midst of the land, saying, Why should the kings of Assyria come, and find much water?
5 Also he strengthened himself, and built up all the wall that was broken, and raised it up to the towers, and another wall without, and repaired Millo in the city of David, and made darts and shields in abundance.
6 And he set captains of war over the people, and gathered them together to him in the street of the gate of the city, and spake comfortably to them, saying,
7 Be strong and courageous, be not afraid nor dismayed for the king of Assyria, nor for all the multitude that is with him: for there be more with us than with him:
8 With him is an arm of flesh; but with us is the LORD our God to help us, and to fight our battles. And the people rested themselves upon the words of Hezekiah king of Judah.
9 After this did Sennacherib king of Assyria send his servants to Jerusalem, (but he himself laid siege against Lachish, and all his power with him,) unto Hezekiah king of Judah, and unto all Judah that were at Jerusalem, saying,
10 Thus saith Sennacherib king of Assyria, Whereon do ye trust, that ye abide in the siege in Jerusalem?
11 Doth not Hezekiah persuade you to give over yourselves to die by famine and by thirst, saying, The LORD our God shall deliver us out of the hand of the king of Assyria?
12 Hath not the same Hezekiah taken away his high places and his altars, and commanded Judah and Jerusalem, saying, Ye shall worship before one altar, and burn incense upon it?
13 Know ye not what I and my fathers have done unto all the people of other lands? were the gods of the nations of those lands any ways able to deliver their lands out of mine hand?
14 Who was there among all the gods of those nations that my fathers utterly destroyed, that could deliver his people out of mine hand, that your God should be able to deliver you out of mine hand?
15 Now therefore let not Hezekiah deceive you, nor persuade you on this manner, neither yet believe him: for no god of any nation or kingdom was able to deliver his people out of mine hand, and out of the hand of my fathers: how much less shall your God deliver you out of mine hand?
16 And his servants spake yet more against the LORD God, and against his servant Hezekiah.
17 He wrote also letters to rail on the LORD God of Israel, and to speak against him, saying, As the gods of the nations of other lands have not delivered their people out of mine hand, so shall not the God of Hezekiah deliver his people out of mine hand.
18 Then they cried with a loud voice in the Jews' speech unto the people of Jerusalem that were on the wall, to affright them, and to trouble them; that they might take the city.
19 And they spake against the God of Jerusalem, as against the gods of the people of the earth, which were the work of the hands of man.
20 And for this cause Hezekiah the king, and the prophet Isaiah the son of Amoz, prayed and cried to heaven.
21 And the LORD sent an angel, which cut off all the mighty men of valour, and the leaders and captains in the camp of the king of Assyria. So he returned with shame of face to his own land. And when he was come into the house of his god, they that came forth of his own bowels slew him there with the sword.
22 Thus the LORD saved Hezekiah and the inhabitants of Jerusalem from the hand of Sennacherib the king of Assyria, and from the hand of all other, and guided them on every side.
23 And many brought gifts unto the LORD to Jerusalem, and presents to Hezekiah king of Judah: so that he was magnified in the sight of all nations from thenceforth.
24 In those days Hezekiah was sick to the death, and prayed unto the LORD: and he spake unto him, and he gave him a sign.
25 But Hezekiah rendered not again according to the benefit done unto him; for his heart was lifted up: therefore there was wrath upon him, and upon Judah and Jerusalem.
26 Notwithstanding Hezekiah humbled himself for the pride of his heart, both he and the inhabitants of Jerusalem, so that the wrath of the LORD came not upon them in the days of Hezekiah.
27 And Hezekiah had exceeding much riches and honour: and he made himself treasuries for silver, and for gold, and for precious stones, and for spices, and for shields, and for all manner of pleasant jewels;
28 Storehouses also for the increase of corn, and wine, and oil; and stalls for all manner of beasts, and cotes for flocks.
29 Moreover he provided him cities, and possessions of flocks and herds in abundance: for God had given him substance very much.
30 This same Hezekiah also stopped the upper watercourse of Gihon, and brought it straight down to the west side of the city of David. And Hezekiah prospered in all his works.
31 Howbeit in the business of the ambassadors of the princes of Babylon, who sent unto him to enquire of the wonder that was done in the land, God left him, to try him, that he might know all that was in his heart.
32 Now the rest of the acts of Hezekiah, and his goodness, behold, they are written in the vision of Isaiah the prophet, the son of Amoz, and in the book of the kings of Judah and Israel.
33 And Hezekiah slept with his fathers, and they buried him in the chiefest of the sepulchres of the sons of David: and all Judah and the inhabitants of Jerusalem did him honour at his death. And Manasseh his son reigned in his stead.


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Product Style: 4E4536
Colour code: Evie
This girls denim shorts made with a soft and stretchy organic cotton fabric for maximum style and comfort, featuring five pockets and the brand iconic brand logo patch at the back
• Girlfriend Shorty
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• 98% cotton, 2% elastane
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Dolce & Gabbana Elegant Red & Black Cotton Square Scarf
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- Material: 100% Cotton
- Color: Black and Red
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Dog Training Near Me Madison, IN.
Dog Training in Madison, IN
In the scenic town of Madison, IN, are you in search of specialized puppy training classes that distinguish themselves from conventional Petsmart or Petco dog training programs? Look no further than Askdogtrainers.com, your premier virtual online dog training school.
Our comprehensive range of dog training services in Madison, IN ensures a unique and tailored approach to cater to the diverse needs of canine companions.Residing in Madison, IN, and in need of expert dog training advice? Turn to Jason Lake, a seasoned online dog trainer with over 20 years of experience, offering a plethora of effective dog training techniques to enhance the bond with your furry companion.
While our expertise lies in fundamental canine behaviors, behavior modification, and competitive obedience training, we also excel in providing instruction for brain training exercises designed to stimulate your dog's motivation and engagement.
This holistic approach to dog training sets us apart, ensuring not only the refinement of basic behaviors and competitive obedience but also delving into the cognitive aspects that contribute to a well-rounded and motivated canine companion. Our commitment is to go beyond the traditional boundaries of dog training, offering a comprehensive program that nurtures both the physical and mental well-being of your furry friend.
Through our specialized brain training exercises, your dog will not only learn essential commands but also develop problem-solving skills, enhance memory, and foster a deeper connection with you. Our trainers, well-versed in the latest techniques and backed by years of experience, tailor each session to cater to the unique needs of your canine companion.
Join us on this transformative journey where your dog's potential is unlocked through a blend of traditional training methods and innovative brain exercises. Elevate the training experience for your furry friend and witness the joy of a well-trained and mentally stimulated dog.
Common Questions:
Question: Do you physically come to my home in Madison, IN
Answer: Askdogtrainers.com offers in-home dog training way of virtual sessions whether you live in or outside of Madison, IN.
Question: After our training session would you be able to help me find a dog trainer that uses your same methods here in Madison, IN?
Answer: I started Askdogtrainers.com in order to have the opportunity to assist dogs and their owners wherever they may be in the world. If your dog has a need that requires hands on and cannot be worked on with virtual dog training, than we would be honored to help you find a professional dog trainer in your area that utilizes the same methods as we do and that we would use with own dogs.
Question: Can I recommend Askdogtrainers.com to my friends and family in Madison, IN?
Answer: We are proud of our services and the fact that we get to help so many families with their dogs were ever they may be located. Recommendations and referrals are always greatly appreciated.
Question: I do not currently have a dog but I'm interested in finding one. Is this a service you can provide even though I live in Madison, IN?
Answer: Yes! Our services are not limited to behavioral or training solutions. Whether you are searching for a German Shepherd Dog, Labrador, Doodle, Rottweiler or any other breeds we can help you find the perfect purebred or mixed breed dog in or around Madison, IN.
Why Choose Askdogtrainers.com?
One of the most common questions we encounter from pet owners is, "Where can I find Dog Training Near Me?" Look no further than Askdogtrainers.com, your ultimate solution for locating top-notch dog training services in your area. We take immense pride in assisting our clients in nurturing stronger bonds with their furry companions, and we're thrilled to receive daily updates filled with heartwarming dog pictures from our satisfied customers.New Puppy in the Family?
If you've recently welcomed a new puppy into your home and are in search of comprehensive puppy training, Askdogtrainers.com is the perfect destination for you. Our expertise extends to every aspect of puppy care, from addressing biting issues to teaching the art of crate training a puppy.Experience Our Virtual Expertise
While Askdogtrainers.com operates as a virtual dog training company, we bring decades of experience gained from teaching dog training classes right to your doorstep, no matter where you are in the world. Even if you're uncertain about how to train a dog from start to finish, our virtual presence can guide you every step of the way. Whether you're interested in online puppy training classes or one-on-one training sessions focusing on the fundamentals of clicker training dogs, Askdogtrainers.com should be your first choice.The Convenience of Virtual Training
Gone are the days of tirelessly searching for "dog obedience training near me." We've revolutionized dog training by offering our services directly to the comfort of your home, regardless of your location. No more hassles of physically attending sessions at places like Petco dog training. If you're in pursuit of dog training classes near me, consider the convenience of virtual training instead. It's worth noting that Askdogtrainers.com is a sister company of Prodogz Dog Training, a well-established dog training school in Medford, Oregon.Abundant Dog Training Tips
At Askdogtrainers.com, we go beyond just providing training sessions. We offer an array of valuable dog training tips to ensure you feel more confident and successful in your journey with your four-legged companion. From the basics of dog training to more advanced techniques, we've got you covered. Concerned about dog training cost? Virtual training often proves to be significantly more cost-efficient due to lower overhead and unmatched convenience. For those seeking additional resources, we host numerous dog training YouTube videos and offer free dog training techniques on our Facebook page and website.Unparalleled Convenience and Expertise
Askdogtrainers.com is committed to making dog training accessible and effective. Our virtual approach allows us to eliminate the need for you to scour the internet for "Dog Training Near Me." Instead, we bring the expertise directly to your doorstep, making the training process more convenient than ever. Whether you're in a bustling city or a quiet rural area, our virtual training is just a click away.Quality and Cost-Efficiency
Wondering about dog training prices? At Askdogtrainers.com, we understand the importance of affordability without compromising on quality. Virtual training not only reduces overhead costs but also offers a more cost-effective solution compared to traditional in-person classes. Rest assured that you'll receive top-tier training without breaking the bank.A Wealth of Resources
Our commitment to your dog's well-being extends beyond our virtual sessions. We believe in empowering pet owners with knowledge. That's why we provide an extensive library of dog training resources, including informative dog training YouTube videos, free techniques on our website, and a vibrant community on our Facebook page. With Askdogtrainers.com, you're never alone on your journey to becoming the best dog owner you can be.Join the Askdogtrainers.com Community Today!
If you're ready to embark on a rewarding journey of dog training and build a stronger connection with your furry friend, don't hesitate to get in touch with Askdogtrainers.com. We're here to guide you, support you, and provide you with the tools and knowledge you need to ensure a happy and harmonious relationship with your beloved pet.Experience the convenience, affordability, and expertise that sets Askdogtrainers.com apart from the rest. Join our community today and take the first step towards becoming the best dog owner you can be. Your dog deserves it, and so do you.
Teaching Your Dog Not To Resource Guard
Resource guarding refers to dogs who growl, snap or bite when they either have something that they value. Often dog owners create resource guarding inadvertently because of something they read on the Internet or something someone told them.
With step-by-step instructions from Askdogtrainers.com you will learn how to identify resource guarding, take steps to decrease incidence and hopefully reach the point where your dog will feel safe and confident eating, sleeping or playing with toys around you and your family.
Potty Training Your Puppy
Potty training your puppy can not only be frustrating but also time consuming without the right tools. The old days of rubbing your puppy's nose in its feces are a thing of the past.
With help from Askdogtrainers.com you can potty train your puppy in as quick as 3 days utilizing positive reinforcement techniques.
Teaching Your Puppy Not To Bite
Biting is one of the most common Behavioral issues that new puppies owners experience. Inadvertently many dog owners are given miss information that actually make the problem worse.
Askdogtrainers.com utilizes positive reinforcement methods to teach owners how to teach their puppies alternative ways to communicate with them besides the need to bite.
Teaching Your Dog To Stay
Over the past 30 years of working with clients it seems that most struggle with teaching their dog how to remain stationary. If not taught properly dogs can find the word "stay" both unpleasant and aversive. however, if top properly dogs can't find confidence and remaining stationary because it leads to something good.
If you find that your dog does not like to stay or you're having to repeat the command "stay" multiple times then a virtual dog training session from Askdogtrainers.com is just what you need to teach your dog that stay in a confident happy manor.
Teaching Your Dog Not To Be Aggressive
Dogs are aggressive for many different reasons everything from genetics to circumstances with other dogs. We when working with reactive dogs it's important not to use harsh or forceful methods but instead use positive reinforcement along with counterconditioning.
Although working with dog reactivity via virtual sessions can be difficult there are things that the handler can learn in order to not make the problem worse and to Know what questions to ask a potential in person trainer to make sure that they are receiving the correct information.
Teaching Your Dog To Be Leashed Calmly
If your dog is anything like ours the moment you pick up the leash they become overly exuberant and hard to control. It would be unfair to punish the dog for getting excited as it would be no different then to punish a child for being excited about Christmas.
With help from Askdogtrainers.com you will learn how to counter condition your dog to the leash and also teach them to sit and remain calm when being leased.
Teaching Your Dog Boundaries
Whether you want to teach your dog to stay out of a certain area or to not bed at the dinner table creating good boundaries through proper training is crucial.
With assistance from Askdogtrainers.com we can help you teach your dog save boundaries at home using positive reinforcement instead of intimidation and punishment.
Teaching Your Dog Not To Jump
Jumping seems to be the most common problem our clients seem to have with their dogs. Without knowing it most people teach their dogs to jump on them due to improper training.
So if your dog or puppy has a jumping issue let Askdogtrainers.com help you teach them a better way to communicate with a quick one hour virtual session.
Teaching Your Dog Not To Pull On Leash
Does your dog drag you down the road when you take them on walks? Pulling is not only annoying but prolong pulling can cause damage to your dogs trachea and also put you at risk for injury.
Utilizing the services that Askdogtrainers.com provides you will learn the steps to take to teach your dog how to walk properly on the leash without risk to you or your dog.
Teaching Your Dog Not To Steel
Some dogs are notorious for stealing shoes, children's toys and food from the table. Understanding why dogs do this can be the key to preventing this behavior and helping them find another way to get our attention.
Utilizing one of our virtual training sessions you will learn key elements to communicate with your dog in a clear and positive way in order to teach them not to counter surf or pilfer items that do not belong to them.
Teaching Your Dog To Come When Called
A reliable recall is not only important but it could also save your dogs life. to teach a proper recall there are three fundamentals that are crucial. Desire, Reinforcement and Proofing.
With help from Askdogtrainers.com we will give you the skills to help teach your dog to come when called with excitement and enthusiasm. So if your dog is running from you you should be coming to us.
Teaching Your Dog To Down
Nine times out of ten when clients have difficulty getting their dog to down properly they thought their dog to "sit" and then to go into a down. Although sometimes this gonna work it leads to a slow down and also confusion between sitting and downing.
With a virtual dog training session from Askdogtrainers.com we will teach you how to teach your dog how to lay down without having to sit first and to stay in that down without popping back up into a sitting position.
Teaching Your Dog To Drop Things
Do you enjoy playing toys with your dog but your dog does not like to drop the toy? Does your dog steal your shoes or other items and not want to let them go?
With a couple easy training techniques Askdogtrainers.com can assist you with teaching your dog how to drop its toys and other items on command each and every time.
Teaching Your Dog Proper Door Manners
Entering and exiting your home with a large dog that insists on going out the door the same time you do can be quite frustrating. Besides making it cumbersome to leave your house it can also be quite dangerous if your dog runs past you outside when if you live on a busy street or there's other dogs around.
With Askdogtrainers.com easy step program you can learn how to teach your dog to not only wait at the door calmly but also ask permission when to enter and leave your home.
Learning How To Be More Engaging With Your Dog
Engagement is the foundation to successful dog training. Understanding engagement and learning how to create it in your dog will give you the power to harness your dogs full potential and create a stronger relationship which in return will create a more reliable dog with their training.
Askdogtrainers.com trainer Jason Lake is an award-winning dog trainer with over 25 years of experience. Utilizing his techniques and games you'll be given the knowledge and know-how to build a stronger relationship with your dog through engagement.