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Tetracyclines (Systemic)

This monograph includes information on the following:

1) Demeclocycline
2) Doxycycline
3) Minocycline
4) Oxytetracycline  
5) Tetracycline

VA CLASSIFICATION
Demeclocycline
Primary: AM250
Secondary: AP109; CV709

Doxycycline
Primary: AM250
Secondary: AP101; AP109; DE751

Minocycline
Primary: AM250
Secondary: AP109; DE751; MS109

Oxytetracycline
Primary: AM250
Secondary: AP109

Tetracycline
Primary: AM250
Secondary: AP101; AP109; DE751; IP100


Commonly used brand name(s): Achromycin V5; Alti-Doxycycline2; Alti-Minocycline3; Apo-Doxy2; Apo-Doxy-Tabs2; Apo-Minocycline3; Apo-Tetra5; Declomycin1; Doryx2; Doxycin2; Doxytec2; Dynacin3; Gen-Minocycline3; Minocin3; Monodox2; Novo-Doxylin2; Novo-Minocycline3; Novo-Tetra5; Nu-Doxycycline2; Nu-Tetra5; Terramycin4; Vibra-Tabs2; Vibra-Tabs C-Pak2; Vibramycin2.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

Not commercially available in Canada.



Category:


Antibacterial; antiprotozoal—Demeclocycline; Doxycycline; Minocycline; Oxytetracycline;  Tetracycline;

Antiacne agent—Doxycycline; Minocycline (oral); Tetracycline;

Antimalarial; intrapleural sclerosing agent—Doxycycline; Tetracycline;

Antirheumatic—Minocycline (oral);

Diuretic (syndrome of inappropriate antidiuretic hormone)—Demeclocycline;

Indications

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.

Accepted

Acne vulgaris (treatment adjunct)1—Doxycycline, minocycline, and tetracycline are indicated as adjunctive treatments for acne {36} {38} {40}. Doxycycline and minocycline are generally no more effective in the initial treatment of acne, are more likely to cause photosensitivity reaction, and are more expensive than tetracycline; however, doxycycline and minocycline may be taken less frequently per day than tetracycline {11}. Oral minocycline may be more effective in severe or resistant acne, and it may be effective in acne unresponsive to tetracycline or where poor absorption of tetracycline is suspected {43}.

Actinomycosis (treatment)—Systemic tetracyclines are indicated in the treatment of actinomycosis caused by Actinomyces species in patients who cannot take penicillins {03} {36} {38} {39} {40}.

Amebiasis, intestinal (treatment adjunct)—Systemic tetracyclines are indicated as treatment adjuncts for acute intestinal amebiasis {03} {36} {38} {39} {40}.

Anthrax (treatment)—Systemic tetracyclines are indicated in the treatment of anthrax caused by Bacillus anthracis in patients who cannot take penicillins {03} {36} {38} {39} {40}.

Bartonellosis (treatment)1—Systemic tetracyclines are indicated for the treatment of bartonellosis caused by Bartonella bacilliformis {03} {36} {38} {39} {40}.

Brucellosis (treatment)—Systemic tetracyclines, in conjunction with streptomycin, are indicated in the treatment of brucellosis caused by Brucella species {03} {36} {38} {39} {40}.

Chancroid (treatment)—Systemic tetracyclines are indicated in the treatment of chancroid caused by Haemophilus ducreyi {03} {36} {38} {39} {40}.

Cholera (treatment)—Oral doxycycline {36}, oral minocycline {40}, and tetracycline {38} are indicated in the treatment of cholera caused by Vibrio cholerae (Vibrio comma) .

Conjunctivitis, inclusion (treatment)—Oral tetracyclines are indicated in the treatment of inclusion conjunctivitis caused by Chlamydia trachomatis {36} {38} {39} {40}.

Genitourinary tract infections (treatment)—Systemic tetracyclines are indicated in the treatment of genitourinary tract infections as follows: {36} {38} {39} {40}


  Infectious agent 
Infection   Chlamydia trachomatis   Neisseria gonorrhoeae  Ureaplasma urealyticum 
Endocervical infections  Doxycycline Tetracycline  Demeclocycline Doxycycline Minocycline Tetracycline    
Epididymo-orchitis  Doxycycline  Demeclocycline Doxycycline   
Rectal infections  Doxycycline Tetracycline     
Urethral infections   Doxycycline Minocycline Tetracycline   Demeclocycline Doxycycline Minocycline Tetracycline   Doxycycline Minocycline  


Gingivostomatitis, necrotizing ulcerative (treatment)—Systemic tetracyclines are indicated in the treatment of necrotizing ulcerative gingivostomatitis (Vincent"s infection) caused by Fusobacterium fusiforme in patients who cannot take penicillins {03} {36} {38} {39} {40}.

Gonorrhea (treatment)—Systemic tetracyclines are indicated for the treatment of uncomplicated gonorrhea caused by Neisseria gonorrhoeae in patients who cannot take penicillins {03} {36} {38} {39} {40}.

Granuloma inguinale (treatment)—Systemic tetracyclines are indicated in the treatment of granuloma inguinale caused by Calymmatobacterium granulomatis {03} {36} {38} {39} {40}.

Listeriosis (treatment)—Systemic tetracyclines are indicated in the treatment of listeriosis caused by Listeria monocytogenes in patients who cannot take penicillins {03} {36} {38} {39} {40}.

Lymphogranuloma venereum (treatment)—Systemic tetracyclines are indicated in the treatment of lymphogranuloma venereum caused by Chlamydia species {03} {36} {38} {39} {40}.

Malaria (prophylaxis)1—Systemic doxycycline is indicated in the prophylaxis of malaria due to Plasmodium falciparum in travelers going to areas with chloroquine-resistant strains {36}. Doxycycline is also often used for chloroquine-sensitive strains in patients who cannot take chloroquine {109}.

Meningococcal carriers (treatment)1—Oral minocycline is indicated in the treatment of asymptomatic meningococcal carriers to eliminate Neisseria meningitidis from the nasopharynx {40}.

Mycobacterial infections, atypical (treatment) 1—Oral minocycline is indicated in the treatment of infections caused by Mycobacterium marinum {40}.
—Treatment of infections caused by Mycobacterium avium intracellulare {97}, Mycobacterium fortuitum {98} {99} {100} {101}, Mycobacterium haemophilum {102}, Mycobacterium kansasii {103}, or Mycobacterium vaccae {104} with tetracyclines, in combination with other anti-infective agents, has been reported. However, controlled clinical studies need to be done before tetracyclines can be recommended for use in the treatment of these atypical mycobacterial infections {105}.

Plague (treatment)—Systemic tetracyclines are indicated in the treatment of plague caused by Yersinia (Pasteurella) pestis {03} {36} {38} {39} {40}.

Pneumonia, mycoplasmal (treatment)—Systemic tetracyclines are indicated in the treatment of pneumonia and other respiratory tract infections caused by Mycoplasma pneumoniae {03} {36} {38} {39} {40}.

Psittacosis (treatment)—Systemic tetracyclines are indicated in the treatment of psittacosis (ornithosis) caused by Chlamydia psittaci {03} {36} {38} {39} {40}.

Q fever (treatment)
Rickettsial pox (treatment)
Rocky Mountain spotted fever (treatment) or
Typhus infections (treatment)—Systemic tetracyclines are indicated in the treatment of Q fever, rickettsial pox, Rocky Mountain spotted fever (including tick fevers), and typhus infections caused by Rickettsiae {03} {36} {38} {39} {40}.

Relapsing fever (treatment)—Systemic tetracyclines are indicated in the treatment of relapsing fever caused by Borrelia recurrentis {03} {36} {38} {39} {40}.

Respiratory tract infections (treatment)—Systemic tetracyclines are indicated in the treatment of respiratory tract infections caused by susceptible strains of Haemophilus influenzae and Klebsiella species {09} {38} {40} {42}. Doxycycline and minocycline are also indicated for the treatment of upper respiratory tract infections caused by susceptible strains of Streptococcus pneumoniae {40} {42}.
—[Demeclocycline is indicated in the treatment of primary atypical pneumonia {106} .]
—Tetracyclines are not recommended as the first choice of treatment for acute throat infections or any staphylococcal infection {29} {38}.

Skin and soft tissue infections (treatment)—Systemic tetracyclines are indicated in the treatment of skin and soft tissue infections, including burn wound infections, caused by susceptible Staphylococcus aureus strains. However, some USP medical experts do not recommend the use of tetracyclines for infections caused by S. aureus .
—[Systemic tetracyclines are also indicated in the treatment of abscess, furunculosis, impetigo, and pyoderma caused by susceptible Escherichia coli , Proteus species, S. aureus , Staphylococcus epidermidis , or Streptococcus pyogenes strains.]

Syphilis (treatment)—Oral tetracyclines are indicated in the treatment of syphilis caused by Treponema pallidum {03} {36} {38} {39} {40}.

Trachoma (treatment)—Systemic tetracyclines are indicated in the treatment of trachoma caused by C. trachomatis , although the infectious agent is not always eliminated as judged by immunofluorescence {03} {36} {38} {39} {40}.

Tularemia (treatment)—Systemic tetracyclines are indicated in the treatment of tularemia caused by Francisella (Pasteurella) tularensis {03} {36} {38} {39} {40}.

Urinary tract infections, bacterial (treatment)— Systemic tetracyclines are indicated in the treatment of urinary tract infections caused by Klebsiella species {03} {36} {38} {39} {40}.
—[Systemic tetracyclines also are indicated in the treatment of urinary tract infections caused by susceptible E. coli , Enterobacter aerogenes , and Proteus species] {24} {25} {29}.

Yaws (treatment)—Systemic tetracyclines are indicated in the treatment of yaws caused by Treponema pertenue in patients who cannot take penicillins {03} {36} {38} {39} {40}.

[Amebiasis, extraintestinal (treatment)]—Tetracycline, an intraluminal amebicide, is indicated concurrently or sequentially with metronidazole in the treatment of extraintestinal amebiasis caused by Entamoeba histolytica . {16}

[Arthritis, gonococcal (treatment) ]1—Systemic tetracyclines are indicated in the treatment of gonococcal arthritis caused by susceptible strains of Neisseria gonorrhoeae in patients who cannot take more appropriate medications {73} {74} {105}.

[Arthritis, rheumatoid (treatment) ]1—Oral minocycline is indicated in the treatment of early (< 2 years), mild rheumatoid arthritis {01} {08} {10} {12}.

[Chlamydial infections (treatment) ]1—Systemic tetracycline is indicated in the treatment of chlamydial infections {50} (Evidence rating: III).

[Enterocolitis, Shigella species (prophylaxis and treatment)]1—Doxycycline is indicated in the prophylaxis and treatment of enterocolitis (shigellosis) caused by susceptible Shigella species {75} {76} {105}.

[Gallbladder infections (treatment)]—Minocycline is indicated in the treatment of gallbladder infections caused by E. coli {29}.

[Leprosy (treatment)]1—Minocycline, in combination with other anti-infective agents, is indicated as an alternative agent (alone or in combination with other appropriate agents) in the treatment of lepromatous leprosy caused by Mycobacterium leprae {94} {95} {96} {105}.

[Lyme disease (treatment)]1—Doxycycline {46} {47} {48} {49} and tetracycline {47} {48} {49} are indicated in the treatment of early Lyme disease caused by Borrelia burgdorferi .

[Malaria (treatment)]1—Oral doxycycline and tetracycline, in combination with antimalarial agents such as quinine, are indicated in the treatment of malaria caused by Plasmodium falciparum {77} {78} {79} {80} {105}.

[Malignant effusions, pleural (treatment) ]1—Doxycycline is indicated as a sclerosing agent in the treatment of malignant pleural effusions by instillation into the pleural cavity {13} {44} {45}.

[Nocardiosis (treatment)]1—Doxycycline and minocycline are indicated as alternative agents in the treatment of nocardiosis in patients who cannot take sulfa medications {81} {82} {83} {84} {105}.

[Pneumothorax (prophylaxis)]1—Tetracycline is indicated as an alternative intrapleural sclerosing agent for the prophylaxis of recurrent, spontaneous pneumothorax {85} {86} {87} {88} {105}. Some clinicians are using doxycycline because parenteral tetracycline is no longer commercially available {107}. Chemical pleurodesis should often be accompanied by bullectomy {108}.

[Rosacea, ocular (treatment)]1—Oral doxycycline and tetracycline are indicated in the treatment of ocular rosacea {89} {90} {91} {105} .

[Syndrome of inappropriate antidiuretic hormone (SIADH) (treatment)]1— Demeclocycline is indicated in the treatment of syndrome of inappropriate (excess) antidiuretic hormone (SIADH) {66} {67} {68}.

[Travelers" diarrhea (treatment)]—Doxycycline can be used in the treatment of travelers" diarrhea caused by susceptible strains of enterotoxigenic Escherichia coli , Salmonella species, and Shigella species in high-risk patients in whom diarrhea and dehydration may result in serious consequences because of chronic underlying health problems {25}. However, doxycycline is generally not used as a first choice of therapy for this indication. {110}

—Tetracyclines are indicated in the treatment of infections due to N. gonorrhoeae in patients who cannot take penicillins {36} {38} {39} {40}. Tetracyclines are also indicated in the treatment of infections due to Campylobacter (Vibrio) fetus or Clostridium species {36} {38} {39} {40}.

—Demeclocycline, doxycycline, and tetracycline are indicated in the treatment of infections due to Bacteroides species {36} {38} {39}.

—Not all species or strains of a particular organism may be susceptible to a specific tetracycline.

Acceptance not established
Tetracycline is reported to have been used in the treatment of bacterial septicemia in a limited number of patients {92} {93}. However, controlled clinical studies need to be done to establish the role of tetracycline for this indication {105}.

Unaccepted
Oral minocycline is not indicated in the treatment of meningococcal infections {40}.

Use of doxycycline for prophylaxis {69} {70} {71} of travelers" diarrhea is considered obsolete and, therefore, is no longer recommended. {111} Tetracycline resistance is extensive in most areas of the world, and more effective medications are currently available. {72}

1 Not included in Canadian product labeling.



Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    Demeclocycline hydrochloride: 501.32 {34}
    Doxycycline: 462.46 {34}
    Doxycycline hyclate: 1025.89 {34}
    Minocycline hydrochloride: 493.95 {34}
    Oxytetracycline: 496.47 {34}
    Oxytetracycline hydrochloride: 496.9 {34}
    Tetracycline: 444.44 {34}
    Tetracycline hydrochloride: 480.9 {34}

Mechanism of action/Effect:

Antibacterial (systemic); antiprotozoal—Tetracyclines are broad-spectrum bacteriostatic agents that act by inhibiting protein synthesis by blocking the binding of aminoacyl-tRNA (transfer RNA) to the mRNA (messenger RNA)-ribosome complex. Reversible binding occurs primarily at the 30 S ribosomal subunit of susceptible organisms. Bacterial cell wall synthesis is not inhibited.

Diuretic (syndrome of inappropriate antidiuretic hormone [SIADH])—In the treatment of SIADH, demeclocycline acts by inhibiting ADH-induced water reabsorption in the distal portion of the convoluted tubules and collecting ducts of the kidneys, thereby causing water diuresis.

Absorption:


Drug
Absorbed
orally
(%)
Effect of
food on
absorption
Demeclocycline
66
Decreased
Doxycycline
90–100
Insignificant
Minocycline
90–100
Insignificant
Oxytetracycline
58
Decreased
Tetracycline
75–77
Decreased

Distribution:

Doxycycline—Achieves therapeutic concentrations in the eye; prostatic concentrations are approximately 60% of serum concentrations.

Minocycline—Achieves high concentrations in saliva, sputum, and tears.

All tetracyclines—Readily distributed to most body fluids, including bile, sinus secretions, and synovial, pleural, ascitic, and gingival crevicular fluids. Cerebrospinal fluid (CSF) concentrations vary and may achieve 10 to 25% of plasma concentrations following parenteral administration. Concentrations in gingival crevicular fluid may be three to seven times the serum concentrations. Tetracyclines tend to localize in bone, liver, spleen, tumors, and teeth; tetracyclines also cross the placenta and distribute into breast milk.

Biotransformation:

Doxycycline and minocycline are partially inactivated by hepatic metabolism.

Half-life:


Drug
Half-life
Normal (hr)
Anuric (hr)
Demeclocycline
10–17
40–60
Doxycycline
12–22
12–22
Minocycline
11–23
11–23
Oxytetracycline
6–10
47–66
Tetracycline
6–11
57–108

Onset of action:

SIADH (demeclocycline)—24 to 48 hours.

Time to peak concentration:

Tetracycline—2 to 3 days may be necessary to achieve therapeutic concentrations of tetracycline.

Other tetracyclines—2 to 4 hours (oral).

Elimination:
    Renal; unchanged, via glomerular filtration. {63}
    Fecal; unchanged, via biliary secretion, gastrointestinal secretion, or poor absorption. {63}
    Dialysis—Tetracyclines are slowly removed by hemodialysis; however, doxycycline is not removed by hemodialysis. Peritoneal dialysis does not effectively remove tetracyclines. {63}

Note: Gastrointestinal secretion is an important route of excretion when doxycycline is administered to patients with renal function impairment or azotemia {63}.



        Drug
        Volume of distribution *
        (L/kg)
Excretion routes (primary/ secondary [% excreted unchanged])  Protein binding 
        Demeclocycline
        1.79
        Renal/biliary
        (42)
        High (91%)
        Doxycycline
        0.7
        Biliary/renal
        (35)
        High (93%)
        Minocycline
        0.14–0.7
        Biliary/renal
        (5–10)
        Moderate
        (76%)
        Oxytetracycline
        0.9–1.9
        Renal/biliary
        (70)
        Low (35%)
        Tetracycline
        1.3–1.6
        Renal/biliary
        (60)
        Moderate
        (65%)
*         Diffuses readily into most body tissues, fluids, and/or cavities.
         Biliary route involves concentration by the liver and excretion via the bile into the intestine from which partial reabsorption occurs.


Precautions to Consider

Cross-sensitivity and/or related problems

Patients hypersensitive to one tetracycline may be hypersensitive to other tetracyclines also.

Patients hypersensitive to lidocaine, procaine, or other ``caine-type'' local anesthetics may also be hypersensitive to the lidocaine component of oxytetracycline injection.

Pregnancy/Reproduction

Pregnancy—
Tetracyclines cross the placenta; use is not recommended during the last half of pregnancy since tetracyclines may cause permanent discoloration of teeth, enamel hypoplasia, and inhibition of skeletal growth in the fetus. In addition, fatty infiltration of the liver may occur in pregnant women, especially with high intravenous doses.

FDA Pregnancy Category D.

Breast-feeding

Tetracyclines are distributed into breast milk; although tetracyclines may form nonabsorbable complexes with breast-milk calcium, use is not recommended because of the possibility of their causing permanent staining of teeth, enamel hypoplasia, inhibition of linear skeletal growth, photosensitivity reactions, and oral and vaginal thrush in infants. In addition, vestibular disturbances may occur with minocycline.

Pediatrics

In infants and children 8 years of age and younger, tetracyclines may cause permanent staining of teeth, enamel hypoplasia, and a decrease in linear skeletal growth rate. Therefore, use is not recommended in patients in these age groups unless other antibacterials are unlikely to be effective or are contraindicated.

Bulging fontanels have been reported in young infants who received full therapeutic doses of tetracyclines. This side effect disappeared rapidly upon discontinuation of the medication. {52} {59}


Geriatrics


No information is available on the relationship of age to the effects of tetracyclines in geriatric patients.


Dental

Use of systemic tetracyclines during pregnancy or in infants and children 8 years of age and younger may cause permanent discoloration of teeth and enamel hypoplasia. Therefore, use is not recommended in patients in these age groups unless other antibacterials are unlikely to be effective or are contraindicated. Vital bleaching or aesthetic restoration may be required if staining is objectionable.

Systemic tetracyclines also may contribute to the development of oral candidiasis.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

» Antacids or
» Calcium supplements such as calcium carbonate or
» Choline and magnesium salicylates or
» Iron supplements or
» Magnesium salicylate or
» Magnesium-containing laxatives or
Sodium bicarbonate    (concurrent use may result in formation of nonabsorbable complexes; also, concurrent use with antacids or sodium bicarbonate may result in decreased absorption of oral tetracyclines because of increased intragastric pH; patients should be advised not to take these medications within 1 to 3 hours of oral tetracyclines)


Barbiturates or
Carbamazepine or
Phenytoin{63}    (concurrent use with doxycycline may result in decreased doxycycline serum concentrations due to induction of microsomal enzyme activity; adjustment of doxycycline dosage or substitution of another tetracycline may be necessary)


» Cholestyramine or
» Colestipol{64}{65}    (concurrent use with cholestyramine or colestipol may result in binding of oral tetracyclines, thus impairing their absorption; an interval of several hours between administration of cholestyramine or colestipol and oral tetracyclines is recommended)


» Contraceptives, estrogen-containing, oral{53}{54}{55}{56}    (concurrent long-term use with tetracyclines may result in reduced contraceptive reliability and increased incidence of breakthrough bleeding)


Digoxin{04}{05}{06}    (although no cases of clinical toxicity have been reported, concurrent use of oral antibiotics may increase serum digoxin concentrations in some individuals; in these individuals, alteration of the gut flora by antibiotics may diminish digoxin conversion to inactive metabolites, resulting in increased serum digoxin concentrations; although limited data are available, this interaction has been reported with oral use of erythromycins, neomycin, and tetracyclines)


Methoxyflurane{63}    (concurrent use with tetracyclines may increase the potential for nephrotoxicity)


» Penicillins    (since bacteriostatic drugs may interfere with the bactericidal effect of penicillins in the treatment of meningitis or in other situations where a rapid bactericidal effect is necessary, concurrent therapy is not recommended)


Vitamin A{17}{51}{52}    (concurrent use with tetracycline has been reported to cause benign intracranial hypertension)



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With diagnostic test results
Catecholamine determinations, urine{42}    (may produce false elevations of urinary catecholamines because of interfering fluorescence)

With physiology/laboratory test values
Alanine aminotransferase (ALT [SGPT]) and
Alkaline phosphatase and
Amylase and
Aspartate aminotransferase (AST [SGOT])    (serum values may be increased)


Bilirubin    (serum concentrations may be increased)


Blood urea nitrogen (BUN){38}{39}{40}    (antianabolic effect of tetracyclines [except doxycycline] may increase BUN concentrations; in patients with significantly impaired renal function, increased serum concentrations of tetracyclines may lead to azotemia, hyperphosphatemia, and acidosis)


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problems exist
Asthma    (doxycycline calcium oral suspension contains sodium metabisulfite, and oxytetracycline contains sodium formaldehyde sulfoxylate, each of which may form a potential sulfiting agent upon oxidation; sulfite sensitivity may be seen more frequently in asthmatic patients and may cause allergic-type reactions, including anaphylactic symptoms and life-threatening or less-severe asthmatic episodes, in certain susceptible individuals {03} {36})


» Diabetes insipidus, nephrogenic    (demeclocycline induces a reversible nephrogenic diabetes insipidus)


Hepatic function impairment    (doxycycline and minocycline are partially metabolized in the liver; hepatic function impairment may prolong the elimination half-life)


Hypersensitivity to tetracyclines, or ``caine-type'' local anesthetics (e.g., lidocaine)
» Renal function impairment    (the half-life of tetracyclines, except doxycycline or minocycline, is prolonged in patients with renal function impairment)




Side/Adverse Effects

Note: Tetracycline-induced hepatotoxicity is usually seen as a fatty degeneration of the liver. It is more likely to occur in pregnant women, in patients receiving high-dose intravenous therapy, and in patients with renal function impairment. However, hepatotoxicity also has occurred in patients without these predisposing conditions. Tetracycline-induced pancreatitis also has been described in association with hepatotoxicity, and without associated liver disease. {14} {15} {58} {61} {62}

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence more frequent
    
Staining of infants' or children's teeth
    
photosensitivity (increased sensitivity of skin to sunlight)

Incidence less frequent
    
Nephrogenic diabetes insipidus ( greatly increased frequency of urination or amount of urine; increased thirst; unusual tiredness or weakness)—with demeclocycline
    
pigmentation of skin and mucous membranes — primarily with minocycline {63}

Incidence rare
    
Benign intracranial hypertension (anorexia; bulging fontanel in infants; headache; papilledema; visual changes; vomiting){51}{52}{57}{59}{60}
    
hepatotoxicity (abdominal pain; nausea and vomiting; yellowing skin){14}{15}{58}
    
pancreatitis ( abdominal pain; nausea and vomiting){61}{62}



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
CNS toxicity (dizziness; lightheadedness ; unsteadiness)—primarily with minocycline
    
gastrointestinal disturbances (cramps or burning of the stomach; diarrhea; nausea or vomiting)

Incidence less frequent
    
Fungal overgrowth (itching of the rectal or genital areas; sore mouth or tongue)
    
hypertrophy of the papilla (darkened or discolored tongue )





Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Tetracyclines (Systemic) .

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to tetracyclines or to “caine-type” local anesthetics

Pregnancy—Tetracyclines cross the placenta; use is not recommended during the last half of pregnancy since tetracyclines may cause permanent staining of teeth, enamel hypoplasia, and inhibition of skeletal growth in the fetus; also, fatty infiltration of the liver may occur in pregnant women, especially with high intravenous doses





Breast-feeding—Tetracyclines are distributed into breast milk; although tetracyclines may form nonabsorbable complexes with breast-milk calcium, use is not recommended because of the possibility of their causing permanent staining of teeth, enamel hypoplasia, inhibition of linear skeletal growth, photosensitivity reactions, and oral and vaginal thrush in infants





Use in children—In infants and children 8 years of age and younger, tetracyclines may cause permanent discoloration of teeth, enamel hypoplasia, and a decrease in linear skeletal growth rate

Other medications, especially antacids, calcium supplements, cholestyramine, choline and magnesium salicylates, colestipol, estrogen-containing oral contraceptives, iron supplements, magnesium salicylate, magnesium-containing laxatives, or penicillins
Other medical problems, especially nephrogenic diabetes insipidus or renal function impairment

Proper use of this medication
» Not giving to children 8 years of age and younger

Taking with at least a full glass of water while in an upright position, to avoid esophageal ulceration and to decrease gastrointestinal irritation

» Avoiding concurrent use of milk or other dairy products when taking oral demeclocycline, oxytetracycline, and tetracycline; if gastrointestinal irritation occurs, these medicines may be taken with food

Oral doxycycline and minocycline may be taken with food or milk if gastric irritation occurs

» Discarding outdated or decomposed tetracyclines (decomposed products may be toxic)

» Compliance with full course of therapy

» Importance of not missing doses and taking at evenly spaced times

» Proper dosing
Taking as soon as possible; not taking if almost time for next dose; not doubling doses

» Proper storage

Precautions while using this medication
Checking with physician if no improvement of symptoms within a few days (or a few weeks or months for acne patients)

» Concurrent administration of any of the tetracyclines and antacids is not recommended. If concurrent use cannot be avoided, tetracyclines should be taken at least 1 to 3 hours before antacids. Because staggered administration may not be completely reliable, physicians should monitor for continued antibiotic efficacy.

» Concurrent administration of any of the tetracyclines and iron is not recommended. If both medications must be used concurrently, iron salts should be taken not less than three hours before or two hours after the tetracycline dose.

» Use of an alternate or additional method of contraception if concurrently taking estrogen-containing oral contraceptives

Caution if surgery with general anesthesia is required

» Possible photosensitivity reactions

» Caution if dizziness, lightheadedness, or unsteadiness occurs


Side/adverse effects
Signs of potential side effects such as discoloration of infant"s or children"s teeth, photosensitivity, nephrogenic diabetes insipidus (with demeclocycline), pigmentation of skin and mucous membranes (with minocycline), benign intracranial hypertension, hepatotoxicity, and pancreatitis


General Dosing Information
Use of tetracyclines (except doxycycline and minocycline) in patients with impaired renal function is not recommended.
For oral dosage forms only
All tetracyclines should be taken with a full glass (240 mL) of water to avoid esophageal ulceration and to decrease gastrointestinal irritation. In addition, most tetracyclines (except doxycycline and minocycline) should preferably be taken on an empty stomach (either 1 hour before or 2 hours after meals) to obtain optimum serum concentrations.


DEMECLOCYCLINE

Summary of Differences


Indications:
Also used as a diuretic (syndrome of inappropriate antidiuretic hormone [SIADH]).



Pharmacology/pharmacokinetics:
Different mechanism of action in SIADH.



Precautions:
Medical considerations/contraindications—Caution needed in nephrogenic diabetes insipidus.



Side/adverse effects:
May cause greatly increased frequency of urination or amount of urine, increased thirst, or unusual tiredness or weakness (nephrogenic diabetes insipidus).



Oral Dosage Forms

Note: Bracketed uses in the Dosage Forms section refer to categories of use and/or indications that are not included in U.S. product labeling.

The dosing and strengths of the dosage forms available are expressed in terms of demeclocycline hydrochloride.

DEMECLOCYCLINE HYDROCHLORIDE TABLETS USP

Usual adult and adolescent dose
Gonorrhea1
Oral, 600 mg initially, then 300 mg every twelve hours for four days for a total dose of 3 grams {39}.

[Syndrome of inappropriate antidiuretic hormone (SIADH)]1
Oral, 3.25 to 3.75 mg per kg of body weight every six hours {105}.

For all other infections
Oral, 150 mg every six hours; or 300 mg every twelve hours {39}.


Usual adult prescribing limits
1.2 grams per day for SIADH.

Usual pediatric dose
For all infections
Children older than 8 years of age: Oral, 1.65 to 3.3 mg per kg of body weight every six hours; or 3.3 to 6.6 mg per kg of body weight every twelve hours {39}.


Note: Infants and children 8 years of age and younger—All tetracyclines form a stable calcium complex in any bone-forming tissue. As a result, tetracyclines may cause permanent yellow-gray-brown staining of the teeth, as well as enamel hypoplasia. Also, a decrease in linear skeletal growth rate may occur in premature infants. Therefore, use of tetracyclines is not recommended in patients in these age groups unless other medications are unlikely to be effective or are contraindicated.


Strength(s) usually available
U.S.—


150 mg (Rx) [Declomycin (sorbitol)]{39}


300 mg (Rx) [Declomycin (sorbitol)]{39}

Canada—


150 mg (Rx) [Declomycin]{07}


300 mg (Rx) [Declomycin]{07}

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight, light-resistant container.

Auxiliary labeling:
   • Continue medicine for full time of treatment.
   • Do not take within 1 to 3 hours of other medicines, milk, or other dairy products.
   • Avoid too much sun or use of sunlamp.
   • Keep container tightly closed in a dry place.


DOXYCYCLINE

Summary of Differences


Precautions:


Drug interactions and/or related problems—
Interacts with barbiturates, carbamazepine, and phenytoin.

No interaction with methoxyflurane.



Laboratory value alterations—
No increase in BUN concentrations.



Medical considerations/contraindications—
Caution not needed in renal impairment.

Increased sensitivity of asthmatic patients to sodium metabisulfite in doxycycline calcium oral suspension.




General dosing information:
No dosage reduction in renal impairment.

May be taken with food, milk, or carbonated beverages.



Additional Dosing Information
Even though approximately 40% of a dose of doxycycline may be eliminated through the kidneys in patients with normal renal function, patients with impaired renal function do not generally require a reduction in dose since doxycycline alternatively may be eliminated through the liver, biliary tract, and gastrointestinal tract and does not have the antianabolic effect of other tetracyclines.

For oral dosage forms only:    • Doxycycline may be taken with food or milk if gastrointestinal irritation occurs.



Oral Dosage Forms

Note: Bracketed uses in the Dosage Forms section refer to categories of use and/or indications that are not included in U.S. product labeling.

The dosing and strengths of the dosage forms available are expressed in terms of doxycycline base.

DOXYCYCLINE CAPSULES USP

Usual adult and adolescent dose
Endocervical, rectal, or urethral infection, uncomplicated, caused by Chlamydia trachomatis
Oral, 100 mg (base) two times a day for seven days {36}.

Epididymo-orchitis caused by C. trachomatis or Neisseria gonorrhoeae or
Nongonococcal urethritis caused by C. trachomatis or Ureaplasma urealyticum
Oral, 100 mg (base) two times a day for at least ten days {36}.

Gonococcal infections, uncomplicated (except anorectal infections in men)
Oral, 100 mg (base) every twelve hours for seven days; or 300 mg initially, then 300 mg one hour later {36}.

[Lyme disease ]1
Oral, 100 mg (base) two times a day {46} {47} {48} {49}.

Malaria prophylaxis1
Oral, 100 mg (base) once a day. Prophylaxis should begin one to two days before travel to the malarious area and be continued daily during travel and for four weeks after the traveler leaves the malarious area. {36}

Syphilis (early), for penicillin-allergic patients
Oral, 100 mg (base) two times a day for two weeks {36}.

Syphilis (of > 1 year's duration), for penicillin-allergic patients
Oral, 100 mg (base) two times a day for four weeks {36}.

For all other infections
Mild to moderate: Oral, 100 mg (base) every twelve hours on the first day, and 100 mg once a day or 50 mg two times a day thereafter {36}.

Severe: Oral, 100 mg (base) every twelve hours {36}.


Usual adult prescribing limits
600 mg (base) per day for five days in acute gonococcal infections; 300 mg per day for all other infections.

Usual pediatric dose
[Lyme disease ]1
Children older than 8 years of age: Oral, 1 to 2 mg (base) per kg of body weight two times a day {48}.

Malaria (prophylaxis) 1
Children older than 8 years of age: Oral, 2 mg (base) per kg of body weight, up to 100 mg, once a day. Prophylaxis should begin one or two days before travel to the malarious area and be continued daily during travel and for four weeks after the traveler leaves the malarious area. {36}

For all other infections
Children older than 8 years of age and weighing more than 45 kg: See Usual adult and adolescent dose .

Children older than 8 years of age and weighing 45 kg or less: Oral, 2.2 mg (base) per kg of body weight two times a day on the first day; then either 2.2 to 4.4 mg per kg of body weight once a day or 1.1 to 2.2 mg per kg of body weight two times a day {36}.


Note: Infants and children 8 years of age and younger—All tetracyclines form a stable calcium complex in any bone-forming tissue. As a result, tetracyclines may cause permanent yellow-gray-brown staining of the teeth, as well as enamel hypoplasia. Also, a decrease in linear skeletal growth rate may occur in premature infants. Therefore, use of tetracyclines is not recommended in patients in these age groups unless other medications are unlikely to be effective or are contraindicated.


Strength(s) usually available
U.S.—


50 mg (base) [Monodox]{42}


100 mg (base) [Monodox]{42}

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight, light-resistant container.

Auxiliary labeling:
   • Continue medicine for full time of treatment.
   • Do not take within 1 to 3 hours of other medicines.
   • Avoid too much sun or use of sunlamp.
   • Keep container tightly closed in a dry place.


DOXYCYCLINE FOR ORAL SUSPENSION USP

Usual adult and adolescent dose
See Doxycycline Capsules USP .

Usual adult prescribing limits
See Doxycycline Capsules USP .

Usual pediatric dose
See Doxycycline Capsules USP .

Strength(s) usually available
U.S.—


25 mg (base) per 5 mL, when reconstituted according to manufacturer's instructions (Rx) [Vibramycin (methylparaben) ( propylparaben) (sucrose)]{36}

Canada—
Not commercially available.

Packaging and storage:
Prior to reconstitution, store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight, light-resistant container.

Stability:
After reconstitution, suspensions retain their potency for 14 days at room temperature.

Auxiliary labeling:
   • Shake well.
   • Continue medicine for full time of treatment.
   • Do not take within 1 to 3 hours of other medicines.
   • Avoid too much sun or use of sunlamp.
   • Beyond-use date.

Note: When dispensing, include a calibrated liquid-measuring device.



DOXYCYCLINE CALCIUM ORAL SUSPENSION USP

Usual adult and adolescent dose
See Doxycycline Capsules USP .

Usual adult prescribing limits
See Doxycycline Capsules USP .

Usual pediatric dose
See Doxycycline Capsules USP .

Strength(s) usually available
U.S.—


50 mg (base) per 5 mL (Rx) [Vibramycin (butylparaben ) (propylparaben) (sodium metabisulfate) (sorbitol solution)]{36}

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight, light-resistant container. Protect from freezing.

Auxiliary labeling:
   • Shake well.
   • Continue medicine for full time of treatment.
   • Do not take within 1 to 3 hours of other medicines.
   • Avoid too much sun or use of sunlamp.

Note: When dispensing, include a calibrated liquid-measuring device.



DOXYCYCLINE HYCLATE CAPSULES USP

Usual adult and adolescent dose
See Doxycycline Capsules USP .

Usual adult prescribing limits
See Doxycycline Capsules USP .

Usual pediatric dose
See Doxycycline Capsules USP .

Strength(s) usually available
U.S.—


50 mg (base) (Rx) [Vibramycin]{36}[Generic]


100 mg (base) (Rx) [Vibramycin]{36}[Generic]

Canada—


100 mg (base) (Rx) [Alti-Doxycycline]{18} [Apo-Doxy] [Doxycin] [Doxytec (lactose)]{21} [Novo-Doxylin] [Nu-Doxycycline]{23} [Vibramycin]{24}

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight, light-resistant container.

Auxiliary labeling:
   • Continue medicine for full time of treatment.
   • Do not take within 1 to 3 hours of other medicines.
   • Avoid too much sun or use of sunlamp.
   • Keep container tightly closed in a dry place.


DOXYCYCLINE HYCLATE DELAYED-RELEASE CAPSULES USP

Usual adult and adolescent dose
See Doxycycline Capsules USP .

Usual adult prescribing limits
See Doxycycline Capsules USP .

Usual pediatric dose
See Doxycycline Capsules USP .

Strength(s) usually available
U.S.—


100 mg (base) (Rx) [Doryx (lactose)]{41}

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight, light-resistant container.

Auxiliary labeling:
   • Continue medicine for full time of treatment.
   • Do not take within 1 to 3 hours of other medicines.
   • Avoid too much sun or use of sunlamp.
   • Keep container tightly closed in a dry place.
   • Swallow capsules whole.

Note: Doxycycline Delayed-release Capsules USP contain enteric-coated pellets.



DOXYCYCLINE HYCLATE TABLETS USP

Usual adult and adolescent dose
See Doxycycline Capsules USP .

Usual adult prescribing limits
See Doxycycline Capsules USP .

Usual pediatric dose
See Doxycycline Capsules USP .

Strength(s) usually available
U.S.—


100 mg (base) (Rx) [Vibra-Tabs]{36}[Generic]

Canada—


100 mg (base) (Rx) [Alti-Doxycycline]{18} [Apo-Doxy-Tabs]{19} [Doxycin]{20} [Novo-Doxylin]{22} [Nu-Doxycycline]{23} [Vibra-Tabs]{24} [Vibra-Tabs C-Pak]{24}

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight, light-resistant container.

Auxiliary labeling:
   • Continue medicine for full time of treatment.
   • Do not take within 1 to 3 hours of other medicines.
   • Avoid too much sun or use of sunlamp.
   • Keep container tightly closed in a dry place.



Parenteral Dosage Forms

Note: The dosing and strengths of the dosage forms available are expressed in terms of doxycycline base.

DOXYCYCLINE HYCLATE FOR INJECTION USP

Usual adult and adolescent dose
Syphilis (primary and secondary)
Intravenous infusion, 150 mg (base) every twelve hours for at least ten days {37}.

For all other infections
Intravenous infusion, 200 mg (base) once a day or 100 mg every twelve hours for the first day, then 100 to 200 mg once a day; or 50 to 100 mg every twelve hours {37}.


Usual adult prescribing limits
300 mg (base) daily {37}.

Usual pediatric dose
For all infections
Children older than 8 years of age and weighing more than 45 kg: See Usual adult and adolescent dose .

Children older than 8 years of age and weighing 45 kg or less: Intravenous infusion, 4.4 mg (base) per kg of body weight once a day; or 2.2 mg per kg of body weight every twelve hours for the first day, then 2.2 to 4.4 mg per kg of body weight once a day or 1.1 to 2.2 mg per kg of body weight every twelve hours {37}.


Note: Infants and children 8 years of age and younger—All tetracyclines form a stable calcium complex in any bone-forming tissue. As a result, tetracyclines may cause permanent yellow-gray-brown staining of the teeth, as well as enamel hypoplasia. Also, a decrease in linear skeletal growth rate may occur in premature infants. Therefore, use of tetracyclines is not recommended in patients in these age groups unless other medications are unlikely to be effective or are contraindicated.


Size(s) usually available:
U.S.—


100 mg (base) (Rx) [Vibramycin]{37}


200 mg (base) (Rx) [Vibramycin]{37}

Canada—
Not commercially available.

Packaging and storage:
Prior to reconstitution, store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Protect from light.

Preparation of dosage form:
To prepare initial dilution for intravenous use, add 10 mL of sterile water for injection or other suitable diluents (see manufacturer's package insert) to each 100-mg vial or 20 mL of diluent to each 200-mg vial. The resulting solution containing the equivalent of 100 to 200 mg of doxycycline may be further diluted in 100 to 1000 mL or in 200 to 2000 mL of suitable diluent, respectively.

Stability:
After reconstitution, intravenous infusions of doxycycline hyclate retain their potency for 12 hours at room temperature or for 72 hours if refrigerated at concentrations of 100 mcg (0.1 mg) to 1 mg per mL in suitable fluids (see manufacturer's package insert). Intravenous infusions of doxycycline hyclate retain their potency for 6 hours at room temperature at concentrations of 100 mcg (0.1 mg) to 1 mg per mL in lactated Ringer's injection or 5% dextrose and lactated Ringer's injection. Infusions must be protected from direct sunlight during administration.

If frozen immediately after reconstitution with sterile water for injection, solutions at concentrations of 10 mg per mL retain their potency up to 8 weeks at -20 °C (-4 °F). Once thawed, solutions should not be refrozen.

Additional information:
Concentrations less than 100 mcg (0.1 mg) per mL or greater than 1 mg per mL are not recommended.

Infusions may be administered over a 1- to 4-hour period. Avoid rapid administration.

Do not administer intramuscularly or subcutaneously.


MINOCYCLINE

Summary of Differences


Precautions:
Laboratory value alterations—No increase in BUN concentrations.

Medical considerations/contraindications—Caution not needed in renal impairment.



Side/adverse effects:
May cause dizziness, light-headedness, or unsteadiness (central nervous system [CNS] toxicity); and pigmentation of skin and mucous membranes.



General dosing information:
No dosage reduction in renal impairment.

May be taken with food or milk.



Additional Dosing Information
For oral dosage forms only:

o Minocycline may be taken with food or milk if gastrointestinal irritation occurs.


Oral Dosage Forms

Note: Bracketed uses in the Dosage Forms section refer to categories of use and/or indications that are not included in U.S. product labeling.

The dosing and strengths of the dosage forms available are expressed in terms of minocycline base.

MINOCYCLINE HYDROCHLORIDE CAPSULES USP

Usual adult and adolescent dose
Gonococcal infections, uncomplicated
Urethral (in men): Oral, 100 mg (base) every twelve hours for five days {40}.

Infections other than urethral or anorectal (in men): Oral, 200 mg (base) initially, then 100 mg every twelve hours for at least four days {40}.

Infections, urethral, caused by Chlamydia trachomatis or Ureaplasma urealyticum1
Oral, 100 mg (base) every twelve hours for at least seven days {40}.

Meningococcal carriers 1
Oral, 100 mg (base) every twelve hours for five days {40}.

Mycobacterium marinum infections1
Oral, 100 mg (base) every twelve hours for six to eight weeks {40}.

[Rheumatoid arthritis]1
Oral, 100 mg (base) two times a day {10}.

Syphilis
Oral, 200 mg (base) initially, then 100 mg every twelve hours for ten to fifteen days; or 100 to 200 mg initially, then 50 mg every six hours for ten to fifteen days {40}.

For all other infections
Oral, 200 mg (base) initially, then 100 mg every twelve hours; or 100 to 200 mg initially, then 50 mg every six hours {40}.


Usual adult prescribing limits
350 mg (base) the first day; then 200 mg a day.

Usual pediatric dose
For all infections
Children older than 8 years of age: Oral, 4 mg (base) per kg of body weight initially, then 2 mg per kg of body weight every twelve hours.


Note: Infants and children 8 years of age and younger—All tetracyclines form a stable calcium complex in any bone-forming tissue. As a result, tetracyclines may cause permanent yellow-gray-brown staining of the teeth, as well as enamel hypoplasia. Also, a decrease in linear skeletal growth rate may occur in premature infants. Therefore, use of tetracyclines is not recommended in patients in these age groups unless other medications are unlikely to be effective or are contraindicated.


Strength(s) usually available
U.S.—


50 mg (base) (Rx) [Dynacin]{35} [Minocin]{40}[Generic]


100 mg (base) (Rx) [Dynacin]{35} [Minocin]{40}[Generic]

Canada—


50 mg (base) (Rx) [Alti-Minocycline]{26} [Apo-Minocycline]{27} [Gen-Minocycline]{28} [Minocin]{29} [Novo-Minocycline]{30}


100 mg (base) (Rx) [Alti-Minocycline]{26} [Apo-Minocycline]{27} [Gen-Minocycline]{28} [Minocin]{29} [Novo-Minocycline]{30}

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight, light-resistant container.

Auxiliary labeling:
   • Continue medicine for full time of treatment.
   • Do not take within 1 to 3 hours of other medicines.
   • Avoid too much sun or use of sunlamp.
   • Keep container tightly closed in a dry place.
   • May cause dizziness.


MINOCYCLINE HYDROCHLORIDE ORAL SUSPENSION USP

Usual adult and adolescent dose
See Minocycline Hydrochloride Capsules USP .

Usual adult prescribing limits
See Minocycline Hydrochloride Capsules USP .

Usual pediatric dose
See Minocycline Hydrochloride Capsules USP .

Strength(s) usually available
U.S.—


50 mg (base) (Rx) [Minocin (alcohol 5% v/v) (butylparaben 0.06%) (propylparaben 0.1%)]

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight, light-resistant container. Protect from freezing.

Auxiliary labeling:
   • Shake well.
   • Continue medicine for full time of treatment.
   • Do not take within 1 to 3 hours of other medicines.
   • Avoid too much sun or use of sunlamp.
   • May cause dizziness.

Note: When dispensing, include a calibrated liquid-measuring device.




Parenteral Dosage Forms

Note: The dosing and strengths of the dosage forms available are expressed in terms of minocycline base.

MINOCYCLINE FOR INJECTION USP

Usual adult and adolescent dose
Intravenous infusion, 200 mg (base) initially, then 100 mg every twelve hours.

Usual adult prescribing limits
400 mg (base) daily.

Usual pediatric dose
For all infections
Children older than 8 years of age: Intravenous infusion, 4 mg (base) per kg of body weight initially, then 2 mg per kg of body weight every twelve hours.


Note: Infants and children 8 years of age and younger—All tetracyclines form a stable calcium complex in any bone-forming tissue. As a result, tetracyclines may cause permanent yellow-gray-brown staining of the teeth, as well as enamel hypoplasia. Also, a decrease in linear skeletal growth rate may occur in premature infants. Therefore, use of tetracyclines is not recommended in patients in these age groups unless other medications are unlikely to be effective or are contraindicated.


Size(s) usually available:
U.S.—


100 mg (base) (Rx) [Minocin]

Canada—
Not commercially available.

Packaging and storage:
Prior to reconstitution, store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Protect from light.

Preparation of dosage form:
To prepare initial dilution for intravenous use, add 5 to 10 mL of sterile water for injection to each 100-mg vial.

The resulting solution may be further diluted in 500 to 1000 mL of 0.9% sodium chloride injection, dextrose injection, dextrose and sodium chloride injection, Ringer's injection, or lactated Ringer's injection, but not in other calcium-containing solutions since a precipitate may form. Administration should be started immediately, but avoid rapid administration.

Stability:
After reconstitution, solutions retain their potency for 24 hours at room temperature.


OXYTETRACYCLINE


Additional Dosing Information
For parenteral dosage forms only:    • Serum concentrations should not exceed 15 mcg per mL, especially in pregnant or postpartum patients with pyelonephritis.



Oral Dosage Forms

Note: The dosing and strengths of the dosage forms available are expressed in terms of oxytetracycline base.

OXYTETRACYCLINE HYDROCHLORIDE CAPSULES USP

Usual adult and adolescent dose
Brucellosis
Oral, 500 mg (base) every six hours for three weeks, given concurrently with 1 gram of streptomycin intramuscularly every twelve hours for the first week and once a day for the second week {03}.

Gonorrhea, uncomplicated
Oral, 1.5 grams (base) initially, then 500 mg every six hours for a total dose of 9 grams {03}.

Syphilis
Oral, 500 mg to 1 gram (base) every six hours for ten to fifteen days for a total dose of 30 to 40 grams {03}.

For all other infections
Oral, 250 to 500 mg (base) every six hours {03}.


Usual adult prescribing limits
4 grams (base) daily.

Usual pediatric dose
For all infections
Children older than 8 years of age: Oral, 6.25 to 12.5 mg (base) per kg of body weight every six hours {03}.


Note: Infants and children 8 years of age and younger—All tetracyclines form a stable calcium complex in any bone-forming tissue. As a result, tetracyclines may cause permanent yellow-gray-brown staining of the teeth, as well as enamel hypoplasia. Also, a decrease in linear skeletal growth rate may occur in premature infants. Therefore, use of tetracyclines is not recommended in patients in these age groups unless other medications are unlikely to be effective or are contraindicated.


Strength(s) usually available
U.S.—


250 mg (base) (Rx) [Terramycin]{03}[Generic]

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight, light-resistant container.

Auxiliary labeling:
   • Continue medicine for full time of treatment.
   • Do not take within 1 to 3 hours of other medicines, milk, or other dairy products.
   • Avoid too much sun or use of sunlamp.
   • Keep container tightly closed in a dry place.



Parenteral Dosage Forms

OXYTETRACYCLINE INJECTION USP

Usual adult and adolescent dose
For all infections
Intramuscular, 100 mg every eight hours; 150 mg every twelve hours; or 250 mg once a day {09}.


Usual adult prescribing limits
500 mg daily.

Usual pediatric dose
For all infections
Children older than 8 years of age: Intramuscular, 5 to 8.3 mg per kg of body weight every eight hours; or 7.5 to 12.5 mg per kg of body weight every twelve hours. Maximum daily dose should not exceed 250 mg. {09}


Note: Infants and children 8 years of age and younger—All tetracyclines form a stable calcium complex in any bone-forming tissue. As a result, tetracyclines may cause permanent yellow-gray-brown staining of the teeth, as well as enamel hypoplasia. Also, a decrease in linear skeletal growth rate may occur in premature infants. Therefore, use of tetracyclines is not recommended in patients in these age groups unless other medications are unlikely to be effective or are contraindicated.


Usual pediatric prescribing limits
250 mg per day {09}.

Strength(s) usually available
U.S.—


50 mg per mL (Rx) [Terramycin]{09}


100 mg per 2 mL (Rx) [Terramycin]{09}


250 mg per 2 mL (Rx) [Terramycin]{09}

Note: Injection contains 2% of lidocaine.


Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Protect from light. Protect from freezing.

Additional information:
Cross-sensitivity with other “caine-type” local anesthetics may also occur.

For deep intramuscular use only. Do not administer intravenously.

May cause intense pain and local irritation at the site of intramuscular injections.

Since intramuscular administration of oxytetracycline produces lower serum concentrations than oral administration in recommended doses, patients should be changed to an oral dosage form as soon as feasible.


TETRACYCLINE


Oral Dosage Forms

Note: Bracketed uses in the Dosage Forms section refer to categories of use and/or indications that are not included in U.S. product labeling.
The dosing and strengths of the dosage forms available are expressed in terms of tetracycline hydrochloride.


TETRACYCLINE ORAL SUSPENSION USP

Usual adult and adolescent dose
Antiacne agent
Oral, 500 mg to 2 grams per day in divided doses initially, as adjunctive therapy, in moderate to severe cases. When improvement is noted (usually after three weeks), dosage should be reduced gradually to a maintenance dose of 125 mg to 1 gram per day. Adequate remission of lesions may also be possible with alternate-day or intermittent therapy. {105}

Brucellosis
Oral, 500 mg four times a day for three weeks, in combination with intramuscular streptomycin 1 gram two times a day for the first week and 1 gram once a day for the second week {38}.

Gonorrhea
Oral, 1.5 grams initially, then 500 mg every six hours for four days, for a total dose of 9 grams {38}.

[Lyme disease ]1
Oral, 250 to 500 mg four times a day {47} {48} {49}.

Syphilis
Oral, 30 to 40 grams over a period of ten to fifteen days {38}.

Uncomplicated endocervical, rectal, or urethral infections caused by Chlamydia trachomatis
Oral, 500 mg four times a day for at least seven days {38}.

For all other infections
Oral, 250 to 500 mg every six hours; or 500 mg to 1 gram every twelve hours {38}.


Usual adult prescribing limits
4 grams daily.

Usual pediatric dose
[Lyme disease ]1
Children older than 8 years of age: Oral, 6.25 to 12.5 mg per kg of body weight four times a day {48}.

For all other infections
Children older than 8 years of age: Oral, 6.25 to 12.5 mg per kg of body weight every six hours; or 12.5 to 25 mg per kg of body weight every twelve hours {38}.


Note: Infants and children 8 years of age and younger—All tetracyclines form a stable calcium complex in any bone-forming tissue. As a result, tetracyclines may cause permanent yellow-gray-brown staining of the teeth, as well as enamel hypoplasia. Also, a decrease in linear skeletal growth rate may occur in premature infants. Therefore, use of tetracyclines is not recommended in patients in these age groups unless other medications are unlikely to be effective or are contraindicated.


Strength(s) usually available
U.S.—
Not commercially available.

Canada—


125 mg per 5 mL (Rx) [Novo-Tetra]{31}

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight, light-resistant container. Protect from freezing.

Auxiliary labeling:
   • Shake well.
   • Continue medicine for full time of treatment.
   • Do not take within 1 to 3 hours of other medicines, milk, or other dairy products.
   • Avoid too much sun or use of sunlamp.

Note: When dispensing, include a calibrated liquid-measuring device.



TETRACYCLINE HYDROCHLORIDE CAPSULES USP

Usual adult and adolescent dose
See Tetracycline Oral Suspension USP .

Usual adult prescribing limits
See Tetracycline Oral Suspension USP .

Usual pediatric dose
See Tetracycline Oral Suspension USP .

Strength(s) usually available
U.S.—


250 mg (Rx) [Achromycin V]{38}[Generic]


500 mg (Rx) [Achromycin V]{38}[Generic]

Canada—


250 mg (Rx) [Apo-Tetra]{32} [Novo-Tetra]{31} [Nu-Tetra]{33}

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight, light-resistant container.

Auxiliary labeling:
   • Continue medicine for full time of treatment.
   • Do not take within 1 to 3 hours of other medicines, milk or other dairy products.
   • Avoid too much sun or use of sunlamp.
   • Keep container tightly closed in a dry place.



Revised: 05/14/2001



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  1. Panel comment, 1/99.
  1. Panel comment, 1/99.
  1. Panel comment, 1/99.
  1. Panel comment, 3/99.
  1. Panel comment, 3/99.
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