TETRACYCLINE HYDROCHLORIDE_- tetracycline hydrochloride_capsule

CLINICAL PHARMACOLOGY
Tetracyclines are readily absorbed and are bound to plasma protein 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. Tetracyclines are primarily bacteriostatic and exert their antimicrobial effect by the inhibition of protein synthesis by binding to the 30S ribosomal subunit. Tetracycline is active against a broad 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. Tetracycline has been shown to be active against most isolates of the following bacteria, both in vitro INDICATIONS AND USAGE Gram-negative Bacteria Acinetobacter Bartonella bacilliformis Brucella Campylobacter fetus Enterobacter aerogenes Escherichia coli Francisella tularensis Haemophilus ducreyi Haemophilus influenzae Klebsiella Klebsiella granulomatis Neisseria gonorrhoeae Shigella Vibrio cholerae Yersinia pestis Gram-positive Bacteria Bacillus anthracis Streptococcus pyogenes Streptococcus pneumoniae Staphylococcus aureus Listeria monocytogenes Anaerobes Bacteroides Clostridium Fusobacterium fusiforme Propionibacterium acnes Other Bacteria Actinomyces Borrelia recurrentis Chlamydophila psittaci Chlamydia trachomatis Rickettsiae Treponema pallidum Treponema pallidum pertenue Parasites Entamoeba Balantidium coli Susceptibility Testing For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.
Microbiology
Tetracyclines are primarily bacteriostatic and exert their antimicrobial effect by the inhibition of protein synthesis by binding to the 30S ribosomal subunit. Tetracycline is active against a broad 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. Tetracycline has been shown to be active against most isolates of the following bacteria, both in vitro INDICATIONS AND USAGE Gram-negative Bacteria Acinetobacter Bartonella bacilliformis Brucella Campylobacter fetus Enterobacter aerogenes Escherichia coli Francisella tularensis Haemophilus ducreyi Haemophilus influenzae Klebsiella Klebsiella granulomatis Neisseria gonorrhoeae Shigella Vibrio cholerae Yersinia pestis Gram-positive Bacteria Bacillus anthracis Streptococcus pyogenes Streptococcus pneumoniae Staphylococcus aureus Listeria monocytogenes Anaerobes Bacteroides Clostridium Fusobacterium fusiforme Propionibacterium acnes Other Bacteria Actinomyces Borrelia recurrentis Chlamydophila psittaci Chlamydia trachomatis Rickettsiae Treponema pallidum Treponema pallidum pertenue Parasites Entamoeba Balantidium coli Susceptibility Testing For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.fda.gov/STIC.
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 HCl and tetracycline HCl 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. Rx only Manufactured by: Strides Pharma Science Limited Bengaluru en dash 562106, India. Distributed by: Strides Pharma Inc. East Brunswick, NJ 08816. Revised: 12/2019

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 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 Hemophilus influenzae Lower respiratory tract infections caused by Streptococcus pyogenes Streptococcus pneumoniae Mycoplasma pneumoniae Klebsiella sp Skin and soft tissue infections caused by Streptococcus pyogenes Staphylococcus aureaus Infections caused by rickettsia including Rocky Mountain spotted fever, typhus group infections, Q fever, rickettsialpox. Psittacosis caused by Chlamydophila psittaci Infections caused by Chlamydia trachomatis Granuloma inquinale caused by Klebsiella 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 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 Other infections caused by susceptible gram-negative organisms such as E. coli Enterobacter aerogenes Shigella sp., Acinetobacter sp Klebsiella sp 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 pertenue 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 Infections due to Clostridium

Adults: Usual daily dose, 1 gram as 500 mg twice a day or 250 mg four times a day. Higher doses such as 500 mg four times a day may be required for severe infections or for those infections which do not respond to the smaller doses. For pediatric patients above eight years of age: Usual daily dose, 10 mg/lb to 20 mg/lb (25mg/kg to 50 mg/kg) body weight divided in four equal doses. 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 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. When used in streptococcal infections, therapy should be continued for 10 days. For treatment of brucellosis, 500 mg tetracycline four times a day for three weeks 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 four times a day for 15 days. Syphilis of more than one year's duration (except neurosyphilis), 500 mg four times a day for 30 days. For treatment of gonorrhea, the recommended dose is 500 mg by mouth four times a day for seven days. Uncomplicated urethral, endocervical or rectal infections in adults caused by Chlamydiatrachomatis 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, reduce dosage gradually 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 Carcinogenesis, Mutagenesis, Impairment of Fertility Use in Specific Population In patients with renal impairment (see WARNINGS

Gastrointestinal: Candida 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: WARNINGS Skin: WARNINGS Renal Toxicity: Liver: Hypersensitivity Reactions: Blood: 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.

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

Pregnancy
Teratogenic Effects (see WARNINGS Nonteratogenic Effects (see WARNINGS Pregnant women with renal disease may be more prone to develop tetracycline-associated liver failure.
Nursing Mothers
Because of 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 DOSAGE AND ADMINISTRATION.

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 antibacterials. 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.

WARNINGS
Tooth Development 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 should not be used in this age group, except for anthrax, unless other drugs are not likely to be effective or are contraindicated. Clostridium difficile Associated Diarrhea Clostridium difficile C. difficile C. difficile C. difficile If CDAD is suspected or confirmed, ongoing use of antibacterial drugs not directed against C. difficile C. difficile Photosensitivity Photosensitivity manifested by an exaggerated sunburn reaction has been observed in some individuals taking tetracyclines. Advise patients apt to be exposed to direct sunlight or ultraviolet lights that this reaction can occur with tetracycline drugs. Discontinue treatment at the first evidence of skin erythema. Intracranial Hypertension Intracranial hypertension (IH, pseudotumor cerebri) has been associated with the use of tetracyclines. Clinical manifestations of IH include headache, blurred vision, diplopia, and vision loss; papilledema can be found on fundoscopy. Women of childbearing age who are overweight or have a history of IH are at greater risk for developing tetracycline associated IH. Concomitant use of isotretinoin and tetracycline should be avoided because isotretinoin, a systemic retinoid, is also known to cause pseudotumor cerebri. Although IH typically resolve after discontinuation of treatment, the possibility for permanent visual loss exists. If visual disturbance occurs during treatment, prompt ophthalmologic evaluation is warranted. Since intracranial pressure can remain elevated for weeks after drug cessation patients should be monitored until they stabilize. Skeletal Development 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, apprise the patient of the potential hazard to the fetus. Tetracycline drugs should not be used during pregnancy unless absolutely necessary. Antianabolic Action 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. Laboratory Monitoring for Long-Term Therapy In long-term therapy, perform periodic laboratory evaluation of organ systems, including hematopoietic, renal and hepatic studies. 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.
Carcinogenesis,Mutagenesis, Impairment of Fertility
Long-term animal studies are currently being conducted to determine whether tetracycline hydrochloride has carcinogenic potential. Some related antibacterials (oxytetracycline, minocycline) have shown evidence of oncogenic activity in rats. In two in vitro Tetracycline hydrochloride had no effect on fertility when administered in the diet to male and female rats at a daily intake of approximately 400 mg/kg/day, roughly 8 times the highest recommended human dose based on body surface area.
Labor and Delivery
The effect of tetracyclines on labor and delivery is unknown.
OVERDOSAGE
In case of overdosage, discontinue medication, treat symptomatically and institute supportive measures. Tetracycline is not dialyzable.

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