Label: TETRACYCLINE HYDROCHLORIDE capsule

  • Category: HUMAN PRESCRIPTION DRUG LABEL
  • DEA Schedule: None
  • Marketing Status: Abbreviated New Drug Application

Drug Label Information

Updated December 1, 2010

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  • SPL UNCLASSIFIED SECTION

    For Oral Use

    Rx only

    To reduce the development of drug-resistant bacteria and maintain the effectiveness of tetracycline hydrochloride and other antibacterial drugs, tetracycline hydrochloride should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

  • DESCRIPTION

    Tetracycline is a yellow, odorless, crystalline powder. Tetracycline is stable in air but exposure to strong sunlight causes it to darken. Its potency is affected in solutions of pH below 2 and is rapidly destroyed by alkali hydroxide solutions. Tetracycline is very slightly soluble in water, freely soluble in dilute acid and in alkali hydroxide solutions, sparingly soluble in alcohol, and practically insoluble in chloroform and in ether. The chemical name for tetracycline hydrochloride is 4-(Dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,6,10,12,-12a-pentahydroxy-6-methyl-1,11-dioxo-2-naphthacenecar-boxamide monohydrochloride. Its structural formula is as follows:

    Tetracycline structural formula

    C22H24N208•HCI M.W. 480.90

    Each capsule, for oral administration, contains 250 mg or 500 mg tetracycline hydrochloride. In addition, each capsule contains the following inactive ingredients: colloidal silicon dioxide, pregelatinized starch and stearic acid. The inactive ingredients for the gelatin capsules include: (250 mg) FD&C Yellow No. 6, D&C Yellow No. 10, and titanium dioxide; (500 mg): FD&C Blue No. 1, FD&C Red No. 40, D&C Yellow No. 10, and titanium dioxide.

  • CLINICAL PHARMACOLOGY

    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 in a biologically active form.

    Microbiology

    Tetracyclines are primarily bacteriostatic and exert their antimicrobial effect by the inhibition of protein synthesis. Tetracycline is 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. While in vitro studies have demonstrated the susceptibility of most strains of the following microorganisms, clinical efficacy for infections other than those included in the INDICATIONS AND USAGE section has not been documented.

    Gram-negative Bacteria

    Neisseria gonorrhea

    Haemophilus ducreyi

    Haemophilus influenzae

    Yersinia pestis (formerly Pasteurella pestis)

    Francisella tularensis (formerly Pasteurella tularensis)

    Vibrio cholera (formerly Vibrio comma)

    Bartonella bacilliformis

    Brucella species

    Because many strains of the following groups of gram-negative microorganisms have been shown to be resistant to tetracyclines, culture and susceptibility testing are recommended:

    Escherichia coli

    Klebsiella species

    Enterobacter aerogenes

    Shigella species

    Acinetobacter species (formerly Mima species and Herellea species)

    Bacteroides species

    Gram-positive Bacteria

    Because many strains of the following groups of gram-positive microorganisms have been shown to be resistant to tetracycline, culture and susceptibility testing are recommended. Up to 44 percent of strains of Streptococcus pyogenes and 74 percent of Streptococcus faecalis have been found to be resistant to tetracycline drugs. Therefore, tetracyclines should not be used for streptococcal disease unless the organisms have been demonstrated to be susceptible.

    Streptococcus pyogenes

    Streptococcus pneumoniae

    Enterococcus group (Streptococcus faecalis and Streptococcus faecium)

    Alpha-hemolytic Streptococci (viridans group)

    Other microorganisms

    Chlamydia psittaci

    Chlamydia trachomatis

    Ureaplasma urealyticum

    Borrelia recurrentis

    Treponema pallidum

    Treponema pertenue

    Clostridia species

    Fusobacterium fusiforme

    Actinomyces species

    Bacillus anthraxis

    Propionibacterium acnes

    Entamoeba species

    Balantidium coli

    Susceptibility Testing

    A tetracycline disk may be used to determine microbial susceptibility to drugs in the tetracycline class. If the Kirby-Bauer method of disk susceptibility testing is used, a 30 mcg tetracycline disk should give a zone of at least 19 mm when tested against a tetracycline susceptible bacterial strain. 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.

  • INDICATIONS AND USAGE

    To reduce the development of drug-resistant bacteria and maintain the effectiveness of tetracycline hydrochloride and other antibacterial drugs, tetracycline hydrochloride 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.

    Tetracycline is indicated in the treatment of infections caused by susceptible strains of the designated organisms in the conditions listed below:

    • Upper respiratory tract infections caused by Streptococcus pyogenes, Streptococcus pneumoniae and Hemophilus influenzae. Note: Tetracycline should not be used for streptococcal disease unless the organism has been demonstrated to be susceptible.
    • Lower respiratory tract infections caused by Streptococcus pyogenes, Streptococcus pneumoniae, Mycoplasma pneumoniae (Eaton agent, and Klebsiella sp.)
    • Skin and soft tissue infections caused by Streptococcus pyogenes, Staphylococcus aureaus. (Tetracyclines are not the drugs of choice in the treatment of any type of staphylococcal infections.)
    • Infections caused by rickettsia including Rocky Mountain spotted fever, typhus group infections, Q fever, rickettsialpox.
    • Psittacosis or ornithosis caused by Chlamydia Psittaci.
    • Infections caused by Chlamydia trachomatis such as uncomplicated urethral, endocervical or rectal infections, inclusion conjunctivitis, trachoma, and lymphogranuloma venereum.
    • Granuloma inquinale caused by Calymmatobacterium granulomatis.
    • Relapsing fever caused by Borrelia sp.
    • Bartonellosis caused by Bartonella bacilliformis.
    • Chancroid caused by Hemophilus ducreyi.
    • Tularemia caused by Francisella tularensis.
    • Plaque caused by Yersinia pestis.
    • Cholera caused by Vibrio cholerae.
    • Brucellosis caused by Brucella species (tetracycline may be used in conjunction with an aminoglycoside).
    • Infections due to Campylobacter fetus.
    • As adjunctive therapy in intestinal amebiasis caused by Entamoeba histolytica.
    • Urinary tract infections caused by susceptible strains of Escherichia coli, Klebsiella, etc.
    • Other infections caused by susceptible gram-negative organisms such as E. coli, Enterobacter aerogenes, Shigella sp., Acinetobacter sp., Klebsiella sp., and Bacteroides sp.
    • In severe acne, adjunctive therapy with tetracycline may be useful.

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

    • syphilis and yaws caused by Treponema pallidum and pertenue, respectively,
    • Vincent’s infection caused by Fusobacterium fusiforme,
    • infections caused by Neisseria gonorrhoeae,
    • anthrax caused by Bacillus anthracis,
    • infections due to Listeria monocytogenes,
    • actinomycosis caused by Actinomyces species,
    • infections due to Clostridium species.
  • CONTRAINDICATIONS

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

  • 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 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 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 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. If this drug 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. Tetracycline drugs should not be used during pregnancy unless absolutely necessary.

    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. Patients apt to be exposed to direct sunlight or ultraviolet light should be advised that this reaction can occur with tetracycline drugs. Treatment should be discontinued at the first evidence of skin erythema.

    The antianabolic 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 renal function, higher serum levels of tetracycline may lead to azotemia, hyperphosphatemia and acidosis.

  • PRECAUTIONS

    General

    As with other antibiotics, 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.

    All infections due to Group A beta-hemolytic streptococci should be treated for at least ten days.

    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.

    Prescribing tetracycline 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 should be counseled that antibacterial drugs including tetracycline should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When tetracycline 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 tetracycline or other antibacterial drugs in the future.

    Laboratory Tests

    In venereal diseases, when coexistent syphilis is suspected, dark field examinations should be done before treatment is started and the blood serology repeated monthly for at least four months.

    In long-term therapy, periodic laboratory evaluation of organ systems, including hematopoietic, renal and hepatic studies, should be performed.

    Drug Interactions

    Since bacteriostatic drugs may interfere with the bactericidal action of penicillin, it is advisable to avoid giving tetracycline in conjunction with penicillin or other bactericidal antibiotics.

    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.

    The concurrent use of tetracycline and methoxyflurane has been reported to result in fatal renal toxicity.

    Absorption of tetracyclines is impaired by antacids containing aluminum, calcium or magnesium and preparations containing iron, zinc, or sodium bicarbonate.

    Concurrent use of tetracycline may render oral contraceptives less effective.

    Carcinogenesis, Mutagenesis, Impairment of Fertility

    Long-term animal studies are currently being conducted to determine whether tetracycline hydrochloride has carcinogenic potential. Some related antibiotics (oxytetracycline, minocycline) have shown evidence of oncogenic activity in rats.

    In two in vitro mammalian cell assay systems (L 51784y mouse Iymphoma and Chinese hamster lung cells), there was evidence of mutagenicity at tetracycline hydrochloride concentrations of 60 and 10 mcg/mL, respectively.

    Tetracycline hydrochloride had no effect on fertility when administered in the diet to male and female rats at a daily intake of 25 times the human dose.

    Pregnancy

    Teratogenic Effects

    Pregnancy Category D

    (see WARNINGS)

    Nonteratogenic Effects

    (see WARNINGS)

    Pregnant women with renal disease may be more prone to develop tetracycline-associated liver failure.

    Labor and Delivery

    The effect of tetracyclines on labor and delivery is unknown.

    Nursing Mothers

    Because of the potential for serious adverse reaction in nursing infants from tetracyclines, a decision should be made whether to discontinue the drug, taking into account the importance of the drug to the mother (see WARNINGS).

    Pediatric Use

    See WARNINGS and DOSAGE AND ADMINISTRATION.

  • ADVERSE REACTIONS

    Gastrointestinal: anorexia, nausea, epigastric distress, vomiting, diarrhea, glossitis, black hairy tongue, dysphagia, enterocolitis, and inflammatory lesions (with monilial overgrowth) in the anogenital region.

    Rare instances of esophagitis and esophageal ulceration have been reported in patients receiving particularly the capsule and also the tablet forms of tetracyclines.

    Most of the patients were reported to have taken medication immediately before going to bed (see DOSAGE AND ADMINISTRATION).

    Teeth: permanent discoloration of teeth may be caused during tooth development. Enamel hypoplasia has also been reported (see WARNINGS).

    Skin: maculopapular and erythematous rashes. Exfoliative dermatitis has been reported but is uncommon. Onycholysis and discoloration of the nails have been reported rarely. Photosensitivity is discussed in WARNINGS.

    Renal toxicity: rise in BUN has been reported and is apparently dose related.

    Liver: hepatotoxicity and liver failure have been observed in patients receiving large doses of tetracycline and in tetracycline-treated patients with renal impairment.

    Hypersensitivity reactions: urticaria, angioneurotic edema, anaphylaxis, anaphylactoid purpura, pericarditis, exacerbation of systemic lupus erythematosus, and serum sickness-like reactions, as fever, rash, and arthralgia.

    Blood: hemolytic anemia, thrombocytopenia, thrombocytopenic purpura, neutropenia and eosinophilia have been reported.

    Other: bulging fontanels in infants and intracranial pressure in adults (see PRECAUTIONS-General).

    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.

  • OVERDOSAGE

    In case of overdosage, discontinue medication, treat symptomatically and institute supportive measures. Tetracycline is not dialyzable.

  • DOSAGE AND ADMINISTRATION

    Adults

    Usual daily dose, 1 gram as 500 mg b.i.d. or 250 mg q.i.d. Higher doses such as 500 mg q.i.d. may be required for severe infections or for those infections which do not respond to the smaller doses.

    Children above eight years of age

    Usual daily dose, 10 to 20 mg/lb (25 to 50 mg/kg) body weight divided in four equal doses.

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

    For treatment of brucellosis, 500 mg tetracycline q.i.d. for three weeks should be accompanied by streptomycin, 1 gram intramuscularly twice daily the first week and once daily the second week.

    For the treatment of syphilis in patients allergic to penicillin, the following dosage of tetracycline is recommended: early syphilis (less than one year’s duration)-500 mg q.i.d. for 15 days. Syphilis of more than one year’s duration (except neurosyphilis)-500 mg q.i.d. for 30 days.

    For treatment of gonorrhea, the recommended dose is 500 mg by mouth four times a day for seven days.

    In cases of moderate to severe acne which, in the judgement of the clinician, require long-term treatment, the recommended initial dosage is 1 gram daily in divided doses. When improvement is noted, dosage should be gradually reduced to maintenance levels ranging from 125 mg to 500 mg daily. In some patients it may be possible to maintain adequate remission of lesions with alternate-day or intermittent therapy. Tetracycline therapy of acne should augment the other standard measures known to be of value. Duration of long-term treatment which can safely be recommended has not been established (see WARNINGS and Carcinogenicity, Mutagenicity, Impairment of Fertility).

    Concomitant therapy

    Absorption of tetracycline is impaired by antacids containing aluminum, calcium or magnesium and preparations containing iron, zinc, or sodium bicarbonate.

    Food and some dairy products also interfere with absorption.

    In the treatment of streptococcal infections, a therapeutic dose of tetracycline should be administered for at least ten days.

    In patients with renal impairment (see WARNINGS): total dosage should be decreased by reduction of recommended individual doses and/or by extending time intervals between doses.

    Uncomplicated urethral, endocervical or rectal infections in adults caused by Chlamydia trachomatis: 500 mg, by mouth, four times a day for at least seven days.

    Administration of adequate amounts of fluid with the capsule formulation of tetracycline is recommended to wash down the drug and reduce the risk of esophageal irritation and ulceration (see ADVERSE REACTIONS).

  • HOW SUPPLIED

    Tetracycline Hydrochloride Capsules USP, 250 mg are available as orange opaque and yellow opaque capsules, imprinted with company logo and 2416, containing 250 mg of tetracycline hydrochloride, packaged in bottles of 28 capsules.

    Tetracycline Hydrochloride Capsules USP, 500 mg are available as black and yellow capsules, imprinted with company logo and 2407, containing 500 mg of tetracycline hydrochloride, packaged in bottles of 28, 30, 40, 42, 56and 90 capsules.

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

    Store at 20° to 25°C (68° to 77°F) [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, minocycline, 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 HCI and tetracycline HCI were goitrogenic in rats fed a low iodine diet. This goitrogenic effect was accomplished 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.

    TEVA PHARMACEUTICALS USA

    Sellersville, PA 18960

    Repackaged by:

    REBEL DISTRIBUTORS CORP

    Thousand Oaks, CA 91320

  • PRINCIPAL DISPLAY PANEL

    Tetracycline HCl 500mg

    NDC 21695-640-40

    TETRACYCLINE HYDROCHLORIDE

    Capsules USP

    500 mg

    Each capsule contains:

    tetracycline hydrochloride, USP 500 mg

    Rx only

  • INGREDIENTS AND APPEARANCE
    TETRACYCLINE HYDROCHLORIDE 
    tetracycline hydrochloride capsule
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC:21695-302(NDC:0172-2416)
    Route of AdministrationORAL
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    Tetracycline Hydrochloride (UNII: P6R62377KV) (TETRACYCLINE - UNII:F8VB5M810T) Tetracycline Hydrochloride250 mg
    Inactive Ingredients
    Ingredient NameStrength
    COLLOIDAL SILICON DIOXIDE (UNII: ETJ7Z6XBU4)  
    STARCH, CORN (UNII: O8232NY3SJ)  
    STEARIC ACID (UNII: 4ELV7Z65AP)  
    FD&C YELLOW NO. 6 (UNII: H77VEI93A8)  
    D&C YELLOW NO. 10 (UNII: 35SW5USQ3G)  
    TITANIUM DIOXIDE (UNII: 15FIX9V2JP)  
    Product Characteristics
    ColorORANGE (orange opaque) , YELLOW (yellow opaque) Scoreno score
    ShapeCAPSULESize19mm
    FlavorImprint Code 2416
    Contains    
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC:21695-302-2828 in 1 BOTTLE
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    ANDAANDA06070403/23/2010
    TETRACYCLINE HYDROCHLORIDE 
    tetracycline hydrochloride capsule
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC:21695-640(NDC:0172-2407)
    Route of AdministrationORAL
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    Tetracycline Hydrochloride (UNII: P6R62377KV) (TETRACYCLINE - UNII:F8VB5M810T) Tetracycline Hydrochloride500 mg
    Inactive Ingredients
    Ingredient NameStrength
    COLLOIDAL SILICON DIOXIDE (UNII: ETJ7Z6XBU4)  
    STARCH, CORN (UNII: O8232NY3SJ)  
    STEARIC ACID (UNII: 4ELV7Z65AP)  
    FD&C BLUE NO. 1 (UNII: H3R47K3TBD)  
    FD&C RED NO. 40 (UNII: WZB9127XOA)  
    D&C YELLOW NO. 10 (UNII: 35SW5USQ3G)  
    TITANIUM DIOXIDE (UNII: 15FIX9V2JP)  
    Product Characteristics
    ColorBLACK, YELLOWScoreno score
    ShapeCAPSULESize22mm
    FlavorImprint Code 2407
    Contains    
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC:21695-640-2828 in 1 BOTTLE
    2NDC:21695-640-3030 in 1 BOTTLE
    3NDC:21695-640-4040 in 1 BOTTLE
    4NDC:21695-640-4242 in 1 BOTTLE
    5NDC:21695-640-5656 in 1 BOTTLE
    6NDC:21695-640-9090 in 1 BOTTLE
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    ANDAANDA06070403/23/2010
    Labeler - Rebel Distributors Corp (118802834)
    Establishment
    NameAddressID/FEIBusiness Operations
    Rebel Distributors Corp118802834RELABEL, REPACK