MINOCYCLINE HYDROCHLORIDE

INDICATIONS AND USAGE Minocycline hydrochloride tablets, USP are indicated in the treatment of the following infections due to susceptible strains of the designated microorganisms: 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 caused by Chlamydia trachomatis. Psittacosis (Ornithosis) due to Chlamydophila psittaci. Trachoma caused by Chlamydia trachomatis , although the infectious agent is not always eliminated, as judged by immunofluorescence. Inclusion conjunctivitis caused by Chlamydia trachomatis. Nongonococcal urethritis, endocervical, or rectal infections 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 Klebsiella granulomatis . Minocycline is indicated for the treatment of infections caused by the following gram-negative microorganisms when bacteriologic testing indicates appropriate susceptibility to the drug: Escherichia coli. Klebsiella aerogenes Shigella species . Acinetobacter species . Respiratory tract infections caused by Haemophilus influenzae. Respiratory tract and urinary tract infections caused by Klebsiella species . Minocycline hydrochloride tablets, USP are indicated for the treatment of infections caused by the following gram-positive microorganisms when bacteriologic testing indicates appropriate susceptibility to the drug: Upper respiratory tract infections caused by Streptococcus pneumoniae. Skin and skin structure infections caused by Staphylococcus aureus . (NOTE: Minocycline is not the drug of choice in the treatment of any type of staphylococcal infection.) When penicillin is contraindicated, minocycline is an alternative drug in the treatment of the following infections: Uncomplicated urethritis in men due to Neisseria gonorrhoeae and for the treatment of other 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 anthraci s . Vincent’s infection caused by Fusobacterium fusiforme . Actinomycosis caused by Actinomyces israelii . Infections caused by Clostridium species. In acute intestinal amebiasis , minocycline may be a useful adjunct to amebicides. In severe acne , minocycline may be useful adjunctive therapy. Oral minocycline is indicated in the treatment of asymptomatic carriers of Neisseria meningitidis to eliminate meningococci from the nasopharynx. In order to preserve the usefulness of minocycline in the treatment of asymptomatic meningococcal carriers, diagnostic laboratory procedures, including serotyping and susceptibility testing, should be performed to establish the carrier state and the correct treatment. It is recommended that the prophylactic use of minocycline be reserved for situations in which the risk of meningococcal meningitis is high. Oral minocycline is not indicated for the treatment of meningococcal infection. Although no controlled clinical efficacy studies have been conducted, limited clinical data show that oral minocycline hydrochloride has been used successfully in the treatment of infections caused by Mycobacterium marinum . To reduce the development of drug-resistant bacteria and maintain the effectiveness of minocycline hydrochloride tablets, USP and other antibacterial drugs, minocycline hydrochloride tablets, USP should be used only to treat or prevent infections that are prov…

DOSAGE AND ADMINISTRATION THE USUAL DOSAGE AND FREQUENCY OF ADMINISTRATION OF MINOCYCLINE DIFFER FROM THAT OF THE OTHER TETRACYCLINES. EXCEEDING THE RECOMMENDED DOSAGE MAY RESULT IN AN INCREASED INCIDENCE OF SIDE EFFECTS. Minocycline hydrochloride tablets may be taken with or without food (see CLINICAL PHARMACOLOGY ). Ingestion of adequate amounts of fluids along with capsule and tablet forms of drugs in the tetracycline-class is recommended to reduce the risk of esophageal irritation and ulceration. The tablets should be swallowed whole. For Pediatric Patients above 8 Years of Age Usual pediatric dose: 4 mg/kg initially followed by 2 mg/kg every 12 hours, not to exceed the usual adult dose. Adults The usual dosage of minocycline hydrochloride tablets is 200 mg initially followed by 100 mg every 12 hours. Alternatively, if more frequent doses are preferred, two or four 50 mg tablets may be given initially followed by one 50 mg tablet 4 times daily. Uncomplicated gonococcal infections other than urethritis and anorectal infections in men: 200 mg initially, followed by 100 mg every 12 hours for a minimum of 4 days, with post-therapy cultures within 2 to 3 days. In the treatment of uncomplicated gonococcal urethritis in men, 100 mg every 12 hours for 5 days is recommended. For the treatment of syphilis, the usual dosage of minocycline hydrochloride should be administered over a period of 10 to 15 days. Close follow-up, including laboratory tests, is recommended. In the treatment of meningococcal carrier state, the recommended dosage is 100 mg every 12 hours for 5 days. Mycobacterium marinum infections: Although optimal doses have not been established, 100 mg every 12 hours for 6 to 8 weeks have been used successfully in a limited number of cases. Uncomplicated urethral, endocervical, or rectal infection in adults caused by Chlamydia trachomatis or Ureaplasma urealyticum : 100 mg orally, every 12 hours for at least 7 days. Ingestion of adequate amounts of fluids along with capsule and tablet forms of drugs in the tetracycline-class is recommended to reduce the risk of esophageal irritation and ulceration. The pharmacokinetics of minocycline in patients with renal impairment (CL CR <80 mL/min) have not been fully characterized. Current data are insufficient to determine if a dosage adjustment is warranted. The total daily dosage should not exceed 200 mg in 24 hours. However, due to the antianabolic effect of tetracyclines, BUN and creatinine should be monitored (see WARNINGS-Antianabolic Action ).

WARNINGS Tooth Development Minocycline 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 drug 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. Skeletal Development All tetracyclines form a stable calcium complex in any bone-forming tissue. A decrease in the 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. Use in Pregnancy 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. The safety of minocycline hydrochloride tablets for use during pregnancy has not been established. Dermatologic Reaction Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) including fatal cases have been reported with minocycline use. Fixed drug eruptions have occurred with minocycline and other tetracyclines. Worsening severity upon subsequent administrations, including generalized bullous fixed drug eruption, has been observed with other tetracyclines (see ADVERSE REACTIONS ). If severe skin reactions occur, discontinue minocycline hydrochloride tablets immediately and institute appropriate therapy. Antianabolic Action The antianabolic action of the tetracyclines may cause an increase in blood urea nitrogen (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. Under such conditions, monitoring of creatinine and BUN is recommended, and the total daily dosage should not exceed 200 mg in 24 hours (see DOSAGE AND ADMINISTRATION ). If renal impairment exists, even usual oral or parenteral doses may lead to systemic accumulation of the drug and possible liver toxicity. Photosensitivity Photosensitivity manifested by an exaggerated sunburn reaction has been observed in some individuals taking tetracyclines. This has been reported with minocycline. Central Nervous System Central nervous system side effects including lightheadedness, dizziness, or vertigo have been reported with minocycline therapy. Patients who experience these symptoms should be cautioned about driving vehicles or using hazardous machinery while on minocycline therapy. These symptoms may disappear during therapy and usually disappear rapidly when the drug is discontinued. Clostridium difficile -Associated Diarrhea Clostridium difficile- associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including minocycline 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 diarr…

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

ADVERSE REACTIONS Due to oral minocycline’s virtually complete absorption, side effects to the lower bowel, particularly diarrhea, have been infrequent. The following adverse reactions have been observed in patients receiving tetracyclines: Body as a whole : Fever and discoloration of secretions. Gastrointestinal : Anorexia, nausea, vomiting, diarrhea, dyspepsia, stomatitis, glossitis, dysphagia, enamel hypoplasia, enterocolitis, pseudomembranous colitis, pancreatitis, inflammatory lesions (with monilial overgrowth) in the oral and anogenital regions. Instances of esophagitis and esophageal ulcerations have been reported in patients taking the tetracycline-class antibiotics in capsule and tablet form. Most of these patients took the medication immediately before going to bed (see DOSAGE AND ADMINISTRATION ). Genitourinary : Vulvovaginitis. Hepatic toxicity : Hyperbilirubinemia, hepatic cholestasis, increases in liver enzymes, fatal hepatic failure, and jaundice. Hepatitis, including autoimmune hepatitis, and liver failure have been reported (see PRECAUTIONS ). Skin : Alopecia, erythema nodosum, hyperpigmentation of nails, pruritus, toxic epidermal necrolysis, vasculitis, maculopapular rash and erythematous rash. Exfoliative dermatitis has been reported. Fixed drug eruptions have been reported. Lesions occurring on the glans penis have caused balanitis. Erythema multiforme and Stevens-Johnson syndrome have been reported. Photosensitivity is discussed above (see WARNINGS-Photosensitivity ). Pigmentation of the skin and mucous membranes has been reported. Respiratory : Cough, dyspnea, bronchospasm, exacerbation of asthma, and pneumonitis. Renal toxicity : Interstitial nephritis. Elevations in BUN have been reported and are apparently dose related (see WARNINGS ). Reversible acute renal failure has been reported. Musculoskeletal : Arthralgia, arthritis, bone discoloration, myalgia, joint stiffness, and joint swelling. Hypersensitivity reactions : Urticaria, angioneurotic edema, polyarthralgia, anaphylaxis/anaphylactoid reaction (including shock and fatalities), anaphylactoid purpura, myocarditis, pericarditis, exacerbation of systemic lupus erythematosus and pulmonary infiltrates with eosinophilia have been reported. A transient lupus-like syndrome and serum sickness-like reactions also have been reported. Blood : Agranulocytosis, hemolytic anemia, thrombocytopenia, leukopenia, neutropenia, pancytopenia, and eosinophilia have been reported. Central Nervous System : Convulsions, dizziness, hypesthesia, paresthesia, sedation, and vertigo. Bulging fontanels in infants and benign intracranial hypertension (pseudotumor cerebri) in adults have been reported (see WARNINGS-Intracranial Hypertension ). Headache has also been reported. Other : Thyroid cancer has been reported in the postmarketing setting in association with minocycline products. When minocycline therapy is given over prolonged periods, monitoring for signs of thyroid cancer should be considered. When given over prolonged periods, tetracyclines have been reported to produce brown-black microscopic discoloration of the thyroid gland. Cases of abnormal thyroid function have been reported. Tooth discoloration in children less than 8 years of age (see WARNINGS-Tooth Development ) and also in adults has been reported. Oral cavity discoloration (including tongue, lip, and gum) has been reported. Tinnitus and decreased hearing have been reported in patients on minocycline hydrochloride. The following syndromes have been reported. In some cases, involving these syndromes, death has been reported. As with other serious adverse reactions, if any of these syndromes are recognized, the drug should be discontinued immediately: Hypersensitivity syndrome consisting of cutaneous reaction (such as rash or exfoliative dermatitis), eosinophilia, and one or more of the following: hepatitis, pneumonitis, nephritis, myocarditis, and pericarditis. Fever and lymphadenopathy may be present. Lupus-li…