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demeclocycline hydrochloride tablet
----------DEMECLOCYCLINE HYDROCHLORIDE Tablets, USP
Full Prescribing Information
To reduce the development of drug-resistant bacteria and maintain the effectiveness of demeclocycline hydrochloride tablets and other antibacterial drugs, demeclocycline hydrochloride tablets should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.
Demeclocycline hydrochloride is an antibiotic isolated from a mutant strain of Streptomyces aureofaciens. Chemically it is 7-Chloro-4-(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,6,10,12, 12a-pentahydroxy-1,11-dioxo-2-naphthacenecarboxamide monohydrochloride.
When demeclocycline hydrochloride is given concomitantly with some dairy products, or antacids containing aluminum, calcium, or magnesium, the extent of absorption is reduced by more than 50%.
Demeclocycline hydrochloride penetrates well into various body fluids and tissues. The percent of demeclocycline hydrochloride bound to plasma protein is about 40% using a dialysis equilibrium method and 90% using an ultra-filtration method. Demeclocycline hydrochloride, like other tetracyclines, is concentrated in the liver and excreted into the bile where it is found in much higher concentrations than in the blood. The rate of demeclocycline hydrochloride renal clearance (35 mL/min/1.73 m2) is less than half that of tetracycline. Following a single 150 mg dose of demeclocycline hydrochloride in normal volunteers, 44% (n = 8) was excreted in urine and 13% and 46%, respectively, were excreted in feces in two patients within 96 hours as active drug.
Demeclocycline has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section.
Because many strains of the following groups of gram-negative microorganisms have been shown to be resistant to tetracyclines, culture and susceptibility testing are especially recommended:
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 procedure. Standardized procedures are based on a dilution method (broth or agar) or equivalent with standardized inoculum concentrations and standardized concentrations of demeclocycline hydrochloride or tetracycline powder.1 The MIC values should be interpreted according to the following criteria:
For organisms other than Haemophilus species, Neisseria gonorrhoeae and Streptococcusspecies: 2
For Haemophilus and Streptococcus species: 2
For Neisseria gonorrhoeae: 2
A report of “Susceptible” indicates that the pathogen is likely to be inhibited by usually achievable concentrations of the antimicrobial compound in blood. A report of “Intermediate” indicates that the result should be considered equivocal, and, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high dosage of drug can be used. This category also provides a buffer zone which prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of “Resistant” indicates that usually achievable concentrations of the antimicrobial compound in the blood are unlikely to be inhibitory and that other therapy should be selected.
Standardized susceptibility test procedures require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures. Standard demeclocycline or tetracycline powder should provide the following MIC values: 2
For Haemophilus species:2
For N. gonorrhoeae:2
For Streptococcus species:2
Interpretation should be as stated above for results using dilution techniques. Interpretation involves correlation of the diameter obtained in the disk test with the MIC for demeclocycline hydrochloride or tetracycline.
INDICATIONS & USAGE
To reduce the development of drug-resistant bacteria and maintain the effectiveness of demeclocycline hydrochloride tablets and other antibacterial drugs, demeclocycline hydrochloride tablets 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.
Rocky Mountain spotted fever, typhus fever and the typhus group, Q fever, rickettsialpox, and tick fevers caused by rickettsiae;
THE USE OF DRUGS OF THE TETRACYCLINE CLASS DURING TOOTH DEVELOPMENT (LAST HALF OF PREGNANCY, INFANCY AND CHILDHOOD TO THE AGE OF 8 YEARS) MAY CAUSE PERMANENT DISCOLORATION OF THE TEETH (YELLOW-GRAY-BROWN). This adverse reaction is more common during long-term use of the drugs but has been observed following repeated short-term courses. Enamel hypoplasia has also been reported. TETRACYCLINE DRUGS, THEREFORE, SHOULD NOT BE USED DURING TOOTH DEVELOPMENT UNLESS OTHER DRUGS ARE NOT LIKELY TO BE EFFECTIVE OR ARE CONTRAINDICATED.
All tetracyclines form a stable calcium complex in any bone-forming tissue. A decrease in fibula growth rate has been observed in premature human infants given oral tetracycline in doses of 25 mg/kg every six 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.
The anti-anabolic action of the tetracyclines may cause an increase in BUN. While this is not a problem in those with normal renal function, in patients with significantly impaired function, higher serum levels of tetracycline may lead to azotemia, hyperphosphatemia, and acidosis.
If renal impairment exists, even usual oral or parenteral doses may lead to excessive systemic accumulation of the drug and possible liver toxicity. Under such conditions, lower than usual total doses are indicated and, if therapy is prolonged, serum level determinations of the drug may be advisable.
Photosensitivity manifested by an exaggerated sunburn reaction has been observed in some individuals taking tetracyclines. Phototoxic reactions can occur in individuals taking demeclocycline, and are characterized by severe burns of exposed surfaces resulting from direct exposure of patients to sunlight during therapy with moderate or large doses of demeclocycline. Patients apt to be exposed to direct sunlight or ultraviolet light should be advised that this reaction can occur, and treatment should be discontinued at the first evidence of erythema of the skin.
Administration of demeclocycline hydrochloride has resulted in appearance of the diabetes insipidus syndrome (polyuria, polydipsia and weakness) in some patients on long-term therapy. The syndrome has been shown to be nephrogenic, dose-dependent and reversible on discontinuance of therapy.
Patients who are experiencing central nervous system symptoms associated with demeclocycline therapy, should be cautioned about driving vehicles or using hazardous machinery while on demeclocycline therapy.
Pseudotumor cerebri (benign intracranial hypertension) in adults has been associated with the use of tetracyclines. The usual clinical manifestations are headache and blurred vision. Bulging fontanels have been associated with the use of tetracyclines in infants. While both of these conditions and related symptoms usually resolve soon after discontinuation of the tetracycline, the possibility for permanent sequelae exists.
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 should be instituted.
Incision and drainage or other surgical procedures should be performed in conjunction with antibiotic therapy, when indicated.
Information for Patients
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.
Concurrent use of tetracyclines with oral contraceptives may render oral contraceptives less effective. (See Drug Interactions.)
Patients should be informed that demeclocycline hydrochloride tablets should be taken at least 1 hour before meals or 2 hours after meals. (See DOSAGE AND ADMINISTRATION.)
Unused supplies of tetracycline antibiotics should be discarded by the expiration date.
Patients who are experiencing headache, dizziness, light-headedness, vertigo, or blurred vision while on demeclocycline therapy, should be cautioned about driving vehicles or using hazardous machinery while receiving demeclocycline therapy. (See WARNINGS.)
In venereal diseases when coexistent syphilis is suspected, darkfield examination should be done before treatment is started and the blood serology repeated monthly for at least 4 months.
In long-term therapy, periodic laboratory evaluation of organ systems, including hematopoietic, renal, and hepatic, should be performed.
All patients with gonorrhea should have a serologic test for syphilis at
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 penicillins, it is advisable to avoid giving tetracycline-class drugs in conjunction with penicillin.
Concurrent use of tetracyclines with oral contraceptives may render oral contraceptives less effective.
The concurrent use of tetracyclines and methoxyflurane has been reported to result in fatal renal toxicity.
Absorption of tetracyclines is impaired by antacids containing aluminum, calcium or magnesium, and by iron-containing preparations.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Although mutagenicity studies of demeclocycline hydrochloride have not been conducted, positive results in in vitro mammalian cell assays (i.e., mouse lymphoma and Chinese hamster lung cells) have been reported for related antibiotics (tetracycline hydrochloride and oxytetracycline). (See WARNINGS and ANIMAL PHARMACOLOGY AND ANIMAL TOXICOLOGY.)
Demeclocycline hydrochloride had no effect on fertility when administered in the diet to male and female rats at a daily intake of 45 times the human dose.
Results of animal studies indicate that tetracyclines cross the placenta, are found in fetal tissues, and can have toxic effects on the developing fetus (often related to retardation of skeletal development). Evidence of embryotoxicity has been noted in animals treated early in pregnancy.
Nonteratogenic effects. (See WARNINGS.)
Labor and Delivery
Gastrointestinal: Anorexia, nausea, vomiting, diarrhea, glossitis, dysphagia, enterocolitis, pancreatitis, and inflammatory lesions (with monilial overgrowth) in the anogenital region, increases in liver enzymes, and hepatic toxicity has been reported rarely.
Rarely, hepatitis and liver failure have been reported. These reactions have been caused by both the oral and parenteral administration of tetracyclines.
Instances of esophageal ulcerations have been reported in patients receiving oral tetracyclines. Most of the patients were reported to have taken the medication immediately before lying down. (See DOSAGE AND ADMINISTRATION.)
Skin: Maculopapular and erythematous rashes, erythema multiforme. Exfoliative dermatitis has been reported but is uncommon. Fixed drug eruptions and Stevens-Johnson syndrome have been reported rarely. Lesions occurring on the glans penis have caused balanitis. Pigmentation of the skin and mucous membranes has also been reported. Photosensitivity is discussed above. (See WARNINGS.)
Renal toxicity: Acute renal failure. Rise in BUN has been reported and is apparently dose related. Nephrogenic diabetes insipidus. (See WARNINGS.)
Hypersensitivity reactions: Urticaria, angioneurotic edema, polyarthralgia, anaphylaxis, anaphylactoid purpura, pericarditis, exacerbation of systemic lupus erythematosus, lupus-like syndrome, pulmonary infiltrates with eosinophilia.
Hematologic: Hemolytic anemia, thrombocytopenia, neutropenia and eosinophilia have been reported.
CNS: Pseudotumor cerebri (benign intracranial hypertension) in adults and bulging fontanels in infants (see PRECAUTIONS-General). Dizziness, headache, tinnitus, and visual disturbances have been reported. Myasthenic syndrome has been reported rarely.
Other: When given over prolonged periods, tetracyclines have been reported to produce brown-black microscopic discoloration of thyroid glands. No abnormalities of thyroid function studies are known to occur. Very rare cases of abnormal thyroid function have been reported.
Tooth discoloration has occurred in pediatric patients less than 8 years of age (see WARNINGS), and also has been reported rarely in adults.
In case of overdosage, discontinue medication, treat symptomatically and institute supportive measures. Tetracyclines are not removed in significant quantities by hemodialysis or peritoneal dialysis.
DOSAGE & ADMINISTRATION
Therapy should be continued for at least 24 to 48 hours after symptoms and fever have subsided.
Concomitant therapy: Absorption of tetracyclines is impaired by antacids containing aluminum, calcium, or magnesium, and by iron-containing preparations. Foods and some dairy products also interfere with absorption. Oral forms of tetracycline should be given at least 1 hour before or 2 hours after meals.
In patients with renal impairment: (See WARNINGS.) Tetracyclines should be used cautiously in patients with impaired renal function. Total dosage should be decreased by reduction of recommended individual doses and/or by extending time intervals between doses.
In patients with liver impairment: Tetracyclines should be used cautiously in patients with impaired liver function. Total dosage should be decreased by reduction of recommended individual doses and/or by extending time intervals between doses.
Administration of adequate amounts of fluid with the oral formulations of tetracyclines is recommended to wash down the drugs and reduce the risk of esophageal irritation and ulceration. (See ADVERSE REACTIONS.)
Adults: Usual daily dose - Four divided doses of 150 mg each or two divided doses of 300 mg each.
For pediatric patients above eight years of age: Usual daily dose, 7 to 13 mg per kg body weight per day, depending upon the severity of the disease, divided into two to four doses not to exceed adult dosage of 600 mg per day.
Gonorrhea patients sensitive to penicillin may be treated with demeclocycline administered as an initial oral dose of 600 mg followed by 300 mg every 12 hours for four days to a total of 3 grams.
Demeclocycline hydrochloride tablets, 150 mg, are round, convex, red, film coated tablets, debossed ‘AN’ above ‘54’ on one side and plain on the other, and are supplied as follows:
NDC 65162-554-10 — Bottle of 100
Demeclocycline hydrochloride tablets, 300 mg, are round, convex, pink, film coated tablets, debossed ‘AN 55’ on one side and plain on the other, and are supplied as follows:
NDC 65162-555-48 — Bottle of 48
Store at 20°-25°C (68°-77°F) [See USP Controlled Room Temperature]. Dispense contents with a child-resistant closure (as required) and in a tight, light-resistant container as defined in the USP.
ANIMAL PHARMACOLOGY AND ANIMAL TOXICOLOGY
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.
MF # 639 Rev: 10/07
Revised: 04/2010 Amneal Pharmaceuticals
Reproduced with permission of U.S. National Library of Medicine
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