TETRACYCLINE HYDROCHLORIDE CAPSULES, USP

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.

Neisseria gonorrhea

Haemophilus ducreyi

Haemophilus influenzae

Yersinia pestis (formerly Pasteurella pestis)

Francisella tularensis (formerly Pasterurella 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

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)

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

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 4.0 mcg/mL and intermediate if the MIC is 4.0 to 12.5 mcg/mL.

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 betahemolytic 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.

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.

Since bacteriostatic drug 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.

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 lymphoma and Chinese hamster lung cells), there was evidence of mutagenicity at tetracycline hydrochloride concentrations of 60 and 10 µg/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.

Category D: (See WARNINGS.)

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

The effect of tetracyclines on labor and delivery is unknown.

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 ).

See WARNINGS and DOSAGE AND ADMINISTRATION.

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 section).

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

Maculopapular and erythrematous rashes. Exfoliative dermatitis has been reported but is uncommon. Onycholysis and discoloration of the nails have been reported rarely. Photosensitivity is discussed in WARNINGS  .

Rise in BUN has been reported and is apparently dose related.

Hepatotoxicity and liver failure have been observed in patients receiving large doses of tetracycline and tetracyclinetreated patients with renal impairment.

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

Hemolytic anemia, thrombocytopenia, thrombocytopenic purpura, neutropenia and eosinophilia have been reported.

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.

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.

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 the 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 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 Carcinogenesis, Mutagenesis, Impairment of Fertilit y).

Absorption of tetracyclines 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).