DECLOMYCIN 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.
DECLOMYCIN contains the following inactive ingredients:
Tablets: Alginic Acid, Corn Starch, Ethylcellulose, Hydroxypropyl Methylcellulose, Magnesium Stearate, Red 7, Sorbitol, Titanium Dioxide, Yellow 10 and other ingredients. May also contain Sodium Lauryl Sulfate.
The tetracyclines are primarily bacteriostatic and are thought to exert their antimicrobial effect by the inhibition of protein synthesis. Tetracyclines are active against a wide range of gram-negative and gram-positive organisms.
The drugs in the tetracycline class have closely similar antimicrobial spectra, and cross-resistance among them is common. Microorganisms may be considered susceptible if the MIC (minimum inhibitory concentration) is not more than 4 mcg/mL and intermediate if the MIC is 4 to 12.5 mcg/mL.
Susceptibility plate testing: A tetracycline disc may be used to determine microbial susceptibility to drugs in the tetracycline class. If the Kirby-Bauer method of disc susceptibility testing is used, a 30 mcg tetracycline disc should give a zone of at least 19 mm when tested against a tetracycline-susceptible bacterial strain.
Tetracyclines are readily absorbed and are bound to plasma proteins in varying degrees. 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.
DECLOMYCIN demeclocycline hydrochloride is indicated in infections caused by the following microorganisms:
Rickettsiae: (Rocky Mountain spotted fever, typhus fever and the typhus group, Q fever, rickettsialpox, tick fevers).
Mycoplasma pneumoniae (PPLO, Eaton agent).
Agents of psittacosis and ornithosis.
Agents of lymphogranuloma venereum and granuloma inguinale.
The spirochetal agent of relapsing fever ( Borrelia recurrentis ).
The following gram-negative microorganisms:
Haemophilus ducreyi chancroid
Yersinia pestis and Francisella tularensis, formerly Pasteurella pestis and Pasteurella tularensis,
Bartonella bacilliformis,
Bacteroides species,
Vibrio comma and Vibrio fetus,
Brucella species (in conjunction with streptomycin).
Because many strains of the following groups of microorganisms have been shown to be resistant to tetracyclines, culture and susceptibility testing are recommended.
Demeclocycline is indicated for treatment of infections caused by the following gram-negative microorganisms, when bacteriologic testing indicates appropriate susceptibility to the drug:
Escherichia coli,
Enterobacter aerogenes (formerly Aerobacter aerogenes ),
Shigella species
Mima species and Herellea species
Haemophilus influenzae (respiratory infections),
Klebsiella species (respiratory and urinary infections).
DECLOMYCIN is indicated for treatment of infections caused by the following gram-positive microorganisms when bacteriologic testing indicates appropriate susceptibility to the drug:
Streptococcus species
Up to 44% of strains of Streptococcus pyogenes and 74% of Streptococcus faecalis have been found to be resistant to tetracycline drugs. Therefore, tetracyclines should not be used for streptococcal disease unless the organism has been demonstrated to be sensitive.
For upper respiratory infections due to Group A beta-hemolytic streptococci, penicillin is the usual drug of choice, including prophylaxis of rheumatic fever.
Streptococcus pneumoniae,
Staphylococcus aureus, skin and soft tissue infections.
Tetracyclines are not the drugs of choice in the treatment of any type of staphylococcal infection.
When penicillin is contraindicated, tetracyclines are alternative drugs in the treatment of infections due to:
Neisseria gonorrhoeae,
Treponema pallidum and Treponema pertenue (syphilis and yaws),
Listeria monocytogenes,
Clostridium species,
Bacillus anthracis,
Fusobacterium fusiforme (Vincent's infection),
Actinomyces species
In acute intestinal amebiasis, the tetracyclines may be a useful adjunct to amebicides.
DECLOMYCIN demeclocycline hydrochloride is indicated in the treatment of trachoma, although the infectious agent is not always eliminated, as judged by immunofluorescence.
Inclusion conjunctivitis may be treated with oral tetracyclines or with a combination of oral and topical agents.
This drug is contraindicated in persons who have shown hypersensitivity to any of the tetracyclines or any of the components of the product formulation.
DEMECLOCYCLINE HYDROCHLORIDE, LIKE OTHER TETRACYCLINE-CLASS ANTIBIOTICS, CAN CAUSE FETAL HARM WHEN ADMINISTERED TO A PREGNANT WOMAN. IF ANY TETRACYCLINE IS USED DURING PREGNANCY, OR IF THE PATIENT BECOMES PREGNANT WHILE TAKING THESE DRUGS, THE PATIENT SHOULD BE APPRISED OF THE POTENTIAL HAZARD TO THE FETUS.
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 DECLOMYCIN 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.
All infections due to Group A beta-hemolytic streptococci should be treated for at least ten days.
Interpretation of Bacteriologic Studies: Following a course of therapy, persistence for several days in both urine and blood of bacterio-suppressive levels of demeclocycline may interfere with culture studies. These levels should not be considered therapeutic.
Photosensitivity manifested by an exaggerated sunburn reaction has been observed in some individuals taking tetracyclines. Patients apt to be exposed to direct sunlight of 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 experience central nervous system symptoms while on demecloycline therapy should be cautioned about driving vehicles or using hazardous machinery while receiving demeclocycline therapy.
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 studies should be performed.
All patients with gonorrhea should have a serologic test for syphilis at the time of diagnosis. Patients treated with demeclocycline hydrochloride should have a follow-up serologic test for syphilis after 3 months.
Because the 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.
Long-term studies in animals to evaluate carcinogenic potential of demeclocycline hydrochloride 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).
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 .)
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.
Teratogenic effects. Pregnancy Category D. (See WARNINGS .) 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 .)
Tetracyclines are excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from the tetracyclines, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. (See WARNINGS .)
Not for use in patients younger than eight years of age. (See WARNINGS , PRECAUTIONS ( General subsection) and DOSAGE AND ADMINISTRATION .
The following reactions have been reported in patients receiving tetracyclines:
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. (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.
Therapy should be continued for at least 24 to 48 hours after symptoms and fever have subsided.
Concomitant therapy: of tetracycline 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: 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.
In the treatment of streptococcal infections, a therapeutic dose of demeclocyline should be administered for at least ten days.
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 children above eight years of age: Usual daily dose, 3-6 mg per pound body weight per day, depending upon the severity of the disease, divided into two to four doses.
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.
DECLOMYCIN® demeclocycline hydrochloride Tablets, 150 mg are round, convex, red, film coated tablets, engraved with LL on one side and D11 on the other, are supplied as follows:
NDC 0005-9218-23--Bottle of 100
DECLOMYCIN® demeclocycline hydrochloride Tablets, 300 mg are round, convex, red, film coated tablets, engraved with LL on one side and D12 on the other, are supplied as follows:
NDC 0005-9270-29--Bottle of 48
Store at controlled room temperature 20°-25°C (68-77°F).
Manufactured by:
LEDERLE PHARMACEUTICAL DIVISION
American Cyanamid Company
Pearl River, NY 10965
CI 5189-4 Revised June 13, 2001
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