Doxycycline Information
Doxycycline ()
Doxycycline () Description
Doxycycline () hyclate is a broad-spectrum antibiotic synthetically derived from oxytetracycline. The chemical designation 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. 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.
The structural formula is as follows:
Each tablet for oral administration contains Doxycycline () hyclate equivalent to 100 mg of Doxycycline () (anhydrous). Inactive ingredients are: Colloidal Silicon Dioxide, Corn Starch, Croscarmellose Sodium, Docusate Sodium, Magnesium Stearate, and Microcrystalline Cellulose. Film Coating and Polishing contains: FD&C Blue No. 2, FD&C Yellow No. 6, and Titanium Dioxide.
Doxycycline () 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%/72 hours in individuals with normal function (creatinine clearance about 75 mL/min). This percentage excretion may fall as low as 1-5%/72 hours in individuals with severe renal insufficiency (creatinine clearance below 10 mL/min). Studies have shown no significant difference in serum half-life of Doxycycline () (range 18-22 hours) in individuals with normal and 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 () Indications And Usage
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:
Doxycycline () is also indicated for the treatment of infections caused by the following gram-negative microorganisms:
Because many strains of the following groups of microorganisms have been shown to be resistant to Doxycycline () culture and susceptibility testing are recommended.
Doxycycline () is indicated for treatment of infections caused by the following gram-negative microorganisms, when bacteriologic testing indicates appropriate susceptibility to the drug:
Doxycycline () is indicated for treatment of infections caused by the following gram-positive microorganisms when bacteriologic testing indicates appropriate susceptibility to the drug:
Doxycycline () Contraindications
This drug is contraindicated in persons who have shown hypersensitivity to any of the tetracyclines.
Doxycycline () 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. TETRACYCLINE DRUGS, THEREFORE, SHOULD NOT BE USED IN THIS AGE GROUP, EXCEPT FOR ANTHRAX, INCLUDING INHALATIONAL ANTHRAX (POST-EXPOSURE), UNLESS OTHER DRUGS ARE NOT LIKELY TO BE EFFECTIVE OR ARE CONTRAINDICATED.
If CDAD is suspected or confirmed, ongoing antibiotic use not directed against may need to be discontinued. Appropriate fluid and electrolyte management protein supplementation, antibiotic treatment of , and surgical evaluation should be instituted as clinically indicated.
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.
Doxycycline () Precautions
As with other antibiotic preparations, use of this drug may result in overgrowth of nonsusceptible organisms, including fungi. If superinfection occurs, the antibiotic should be discontinued and appropriate therapy instituted.
Bulging fontanels in infants and benign intracranial hypertension in adults have been reported in individuals receiving tetracyclines. These conditions disappeared when the drug was discontinued.
Incision and drainage or other surgical procedures should be performed in conjunction with antibiotic therapy, when indicated.
Doxycycline () offers substantial but not complete suppression of the asexual blood stages of strains.
Doxycycline () does not suppress sexual blood stage gametocytes. Subjects completing this prophylactic regimen may still transmit the infection to mosquitoes outside endemic areas.
Prescribing Doxycycline () 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.
Patients taking Doxycycline () for malaria prophylaxis should be advised:
All patients taking Doxycycline () should be advised:
Patients should be counseled that antibacterial drugs including Doxycycline () hyclate should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Doxycycline () is 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 or not 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 or other antibacterial drugs in the future.
Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, 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 antibiotic. If this occurs, patients should contact their physician as soon as possible.
In venereal disease, when co-existing 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.
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 tetracycline is impaired by antacids containing aluminum, calcium, or magnesium, and iron-containing preparations.
Absorption of tetracycline 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.
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 antibiotics, oxytetracycline (adrenal and pituitary tumors), and minocycline (thyroid tumors).
Likewise, although mutagenicity studies of Doxycycline () have not been conducted, positive results in mammalian cell assays have been reported for related antibiotics (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.
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 risk.
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 doxycycyline anytime during pregnancy. Sixty-three (0.19%) of the controls and 56 (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 cases.
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.
Doxycycline () Adverse Reactions
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 ).
Skin: maculopapular and erythematous rashes. Exfoliative dermatitis has been reported but is uncommon. Photosensitivity is discussed above. (See ).
Renal toxicity: Rise in BUN has been reported and is apparently dose related. (See ).
Hypersensitivity reactions: urticaria, angioneurotic edema, anaphylaxis, anaphylactoid purpura, serum sickness, pericarditis, and exacerbation of systemic lupus erythematosus.
Blood: Hemolytic anemia, thrombocytopenia, neutropenia, and eosinophilia have been reported.
Other: bulging fontanels in infants and intracranial hypertension in adults. (See ).
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.
Doxycycline () 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.
Doxycycline () Dosage And Administration
Other dosage forms of Doxycycline () may be more appropriate to meet some of the dosing recommendations listed below.
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.
Doxycycline () How Supplied
Doxycycline () Hyclate Tablets USP, equivalent to 100 mg Doxycycline () : Orange Coated, Round, Unscored Tablets, Embossed “WW 112”.
Unit dose packages of 100 (10x10) NDC 62584-693-01
Store at 20°-25°C (68°-77°F) [See USP Controlled Room Temperature]. Protect from light and moisture.
Doxycycline () Animal Pharmacology And Animal Toxicology
Hyperpigementation of the thyroid has been produced by members of the tetracycline class in the following species: in rats by oxytetracycline, Doxycycline () , tetracycline PO and methacycline; in minipigs by Doxycycline () , minocycline, tetracycline PO, and methacycline; in dogs by Doxycycline () and minocycline; in monkeys by minocycline.
Minocycline, tetracycline PO, methacycline, Doxycycline () , tetracycline base, oxytetracycline HCI, and tetracycline HCI 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.
Doxycycline () References
Manufactured By: Eatontown, NJ 07724Revised October 2008
Repackaged by: Columbus, Ohio 43217
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Doxycycline () Principal Display Panel
