Rx only

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.

DESCRIPTION

Demeclocycline hydrochloride USP 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. The structural formula is:

C21H21ClN2O8 • HCl M.W. 501.32

Each film coated tablet, for oral administration, contains 150 mg or 300 mg of demeclocycline hydrochloride USP and has the following inactive ingredients: colloidal silicon dioxide, crospovidone, FD&C Red No. 40, FD&C Yellow No. 6, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polysorbate 80, povidone, sodium stearyl fumarate, and titanium dioxide.

CLINICAL PHARMACOLOGY

INDICATIONS AND USAGE

Demeclocycline hydrochloride USP is indicated in the treatment of infections caused by susceptible strains of the designated microorganisms in the conditions below:

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 due to Chlamydia trachomatis; Psittacosis (Ornithosis) due to Chlamydia psittaci; Trachoma due to Chlamydia trachomatis, although the infectious agent is not always eliminated, as judged by immunofluorescence; Inclusion conjunctivitis caused by Chlamydia trachomatis; Nongonococcal urethritis in adults caused by Ureaplasma urealyticum or Chlamydia trachomatis; Relapsing fever due to Borrelia recurrentis;

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 Calymmatobacterium granulomatis;

Demeclocycline hydrochloride USP 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;

Shigella species;

Acinetobacter species;

Respiratory tract infections caused by Haemophilus influenzae;

Respiratory tract and urinary tract infections caused by Klebsiella species.

Demeclocycline hydrochloride USP 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;

Skin and skin structure infections caused by Staphylococcus aureus.

(Note: Tetracyclines, including demeclocycline, are not the drugs of choice in the treatment of any type of staphylococcal infection.)

When penicillin is contraindicated, tetracyclines, including demeclocycline hydrochloride, are alternative drugs in the treatment of the following infections:

Uncomplicated urethritis in men due to Neisseria gonorrhoeae, and for the treatment of other uncomplicated gonococcal infections;

Infections in women caused by Neisseria gonorrhoeae;

Syphilis caused by Treponema pallidum subspecies pallidum;

Yaws caused by Treponema pallidum subspecies pertenue;

Listeriosis due to Listeria monocytogenes;

Anthrax due to Bacillus anthracis;

Vincent’s infection caused by Fusobacterium fusiforme;

Actinomycosis caused by Actinomyces israelii;

Clostridial diseases caused by Clostridium species.

In acute intestinal amebiasis, demeclocycline hydrochloride USP may be a useful adjunct to amebicides.

In severe acne, demeclocycline hydrochloride USP may be a useful adjunctive therapy.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of demeclocycline hydrochloride tablets USP and other antibacterial drugs, demeclocycline hydrochloride tablets USP should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

CONTRAINDICATIONS

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

WARNINGS

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 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. 

Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including demeclocycline hydrochloride, 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 antibiotic use. 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 antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

PRECAUTIONS

ADVERSE REACTIONS

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 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.

OVERDOSAGE

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 AND ADMINISTRATION

Therapy should be continued for at least 24 to 48 hours after symptoms and fever have subsided.

Concomitant Therapy

Absorption 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

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).

HOW SUPPLIED

Demeclocycline Hydrochloride Tablets USP, 150 mg are available as pink, round, biconvex, film-coated, unscored tablets, debossed with b701 on one side and 150 on the other, packaged in bottle of 100 tablets.

Demeclocycline Hydrochloride Tablets USP, 300 mg are available as pink, round, biconvex, film-coated, unscored tablets, debossed with b702 on one side and 300 on the other,  packaged in bottle of 48 tablets.

Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).

Store at 20º to 25ºC (68º to 77ºF) [See USP Controlled Room Temperature].

ANIMAL PHARMACOLOGY AND ANIMAL TOXICOLOGY

Hyperpigmentation of the thyroid has been produced by members of the tetracycline class in the following species: in rats by oxytetracycline, doxycycline, tetracycline 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.

REFERENCES

1. National Committee for Clinical Laboratory Standards. (2000). “Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. Approved standard M7-A5 and informational supplement M100-S10.” National Committee for Clinical Laboratory Standards, Wayne, PA.
2. National Committee for Clinical Laboratory Standards. (2000). “Performance standards for antimicrobial disk susceptibility tests. Approved standard M2-A7.” National Committee for Clinical Laboratory Standards, Wayne, PA.
3. National Committee for Clinical Laboratory Standards. (2002). “Performance standards for antimicrobial susceptibility testing. Twelfth informational supplement. M100-S12.” National Committee for Clinical Laboratory Standards, Wayne, PA.

TEVA PHARMACEUTICALS USA

Sellersville, PA 18960

Iss. 8/2011

PRINCIPAL DISPLAY PANEL

PRINCIPAL DISPLAY PANEL