Doxycycline

To reduce the development of drug-resistant bacteria and maintain effectiveness of doxycycline tablets and other antibacterial drugs, doxycycline tablets should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Doxycycline tablets are indicated for the treatment of the following infections:

Rocky Mountain spotted fever, typhus fever and the typhus group, Q fever, rickettsialpox, and tick fevers caused by Rickettsiae.

Respiratory tract infections caused by

Lymphogranuloma venereum caused by

Psittacosis (ornithosis) caused by

Trachoma caused by

Inclusion conjunctivitis caused by

Uncomplicated urethral, endocervical or rectal infections in adults caused by

Nongonococcal urethritis caused by

Relapsing fever due to

Doxycycline tablets are also indicated for the treatment of infections caused by the following gram-negative microorganisms:

Chancroid caused by

Plague due to

Tularemia due to

Cholera caused by

Campylobacter fetus infections caused by

Brucellosis due to

Bartonellosis due to

Granuloma inguinale caused by

Because many strains of the following groups of microorganisms have been shown to be resistant to doxycycline, culture and susceptibility testing are recommended.

Doxycycline tablets are indicated for treatment of infections caused by the following gram-negative microorganisms, when bacteriologic testing indicates appropriate susceptibility to the drug:

Respiratory tract infections caused by

Respiratory tract and urinary tract infections caused by

Doxycycline tablets are indicated for treatment of infections caused by the following gram-positive microorganisms when bacteriologic testing indicates appropriate susceptibility to the drug:

Upper respiratory infections caused by

Anthrax due to

When penicillin is contraindicated, doxycycline tablets are an alternative drug in the treatment of the following infections:

Uncomplicated gonorrhea caused by

Syphilis caused by

Yaws caused by

Listeriosis due to

Vincent’s infection caused by

Actinomycosis caused by

Infections caused by

In acute intestinal amebiasis, doxycycline tablets may be a useful adjunct to amebicides.

In severe acne, doxycycline tablets may be useful adjunctive therapy.

THE USUAL DOSAGE AND FREQUENCY OF ADMINISTRATION OF DOXYCYCLINE TABLETS DIFFERS FROM THAT OF THE OTHER TETRACYCLINES. EXCEEDING THE RECOMMENDED DOSAGE MAY RESULT IN AN INCREASED INCIDENCE OF SIDE EFFECTS.

For all pediatric patients weighing less than 45 kg with severe or life-threatening infections (e.g. anthrax, Rocky Mountain spotted fever), the recommended dosage is 2.2 mg/kg of body weight administered every 12 hours. Children weighing 45 kg or more should receive the adult dose (see

For pediatric patients with less severe disease (greater than 8 years of age and weighing less than 45 kg), the recommended dosage schedule is 4.4 mg per kg of body weight divided into two doses on the first day of treatment, followed by a maintenance dose of 2.2 mg per kg of body weight (given as a single daily dose or divided into twice daily doses). For pediatric patients weighing over 45 kg, the usual adult dose should be used.

The therapeutic antibacterial serum activity will usually persist for 24 hours following recommended dosage.

When used in streptococcal infections, therapy should be continued for 10 days.

Administration of adequate amounts of fluid along with capsule and tablet forms of drugs in the tetracycline class is recommended to wash down the drugs and reduce the risk of esophageal irritation and ulceration. (See ADVERSE REACTIONS)

If gastric irritation occurs, it is recommended that doxycycline be given with food or milk. The absorption of doxycycline is not markedly influenced by simultaneous ingestion of food or milk.

Studies to date have indicated that administration of doxycycline at the usual recommended doses does not lead to excessive accumulation of doxycycline in patients with renal impairment.

ADULTS: 100 mg of doxycycline tablets, by mouth, twice a day for 60 days. CHILDREN: weighing less than 100 pounds (45 kg); 1 mg/lb (2.2 mg/kg) of body weight, by mouth, twice a day for 60 days. Children weighing 100 pounds or more should receive the adult dose.

Due to oral doxycycline’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.

When given over prolonged periods, tetracyclines have been reported to produce brown-black microscopic discoloration of the thyroid gland. No abnormalities of thyroid function are known to occur.

Doxycycline is a broad-spectrum antibacterial synthetically derived from oxytetracycline. Doxycycline 150 mg, 100 mg, 75 mg, and 50 mg tablets contain doxycycline monohydrate, USP equivalent to 150 mg, 100 mg, 75 mg, or 50 mg of doxycycline for oral administration. Inactive ingredients include colloidal silicon dioxide, hypromellose, magnesium stearate, microcrystalline cellulose, polysorbate 80, sodium starch glycolate, and titanium dioxide. In addition, doxycycline 50 mg tablets contain: FD&C Blue #1 Aluminum lake and polyethylene glycol, 75 mg tablets contain: D&C Yellow #10 Aluminum lake, FD&C Blue #1 Aluminum lake, FD&C Yellow #6 Aluminum lake and triacetin, 100 mg tablets contain: polyethylene glycol and FD&C Blue #1 Aluminum lake and 150 mg tablets contain: polyethylene glycol. Its molecular weight is 462.46. The chemical designation of the light-yellow crystalline powder is alpha-6-deoxy-5-oxytetracycline.

Structural formula:

C₂₂H₂₄N₂O₈•H₂O

Doxycycline has a high degree of lipid solubility and a low affinity for calcium binding. It is highly stable in normal human serum. Doxycycline will not degrade into an epianhydro form

Tetracyclines are readily absorbed and are bound to plasma proteins in varying degrees. They are concentrated by the liver in the bile and excreted in the urine and feces at high concentrations in a biologically active form. Doxycycline is virtually completely absorbed after oral administration.

Following a 200 mg dose of doxycycline monohydrate, 24 normal adult volunteers averaged the following serum concentration values:

Average Observed Values

Excretion of doxycycline by the kidney is about 40%/72 hours in individuals with normal function (creatinine clearance about 75 mL/min). This percentage excretion may fall as low as 1 to 5%/72 hours in individuals with severe renal insufficiency (creatinine clearance below 10 mL/min). Studies have shown no significant difference in serum half-life of doxycycline (range 18to22 hours) in individuals with normal and severely impaired renal function.

Hemodialysis does not alter serum half-life.

Doxycycline inhibits bacterial protein synthesis by binding to the 30S ribosomal subunit. Doxycycline has bacteriostatic activity against a broad range of Gram-positive and Gram-negative bacteria.

Resistance

Cross resistance with other tetracyclines is common.

Doxycycline has been shown to be active against most isolates of the following microorganisms, both

•  
  Acinetobacter
  species
•  
  Bartonella bacilliformis
•  
  Brucella
  species
•  
  Campylobacter fetus
•  
  Enterobacter aerogenes
•  
  Escherichia coli
•  
  Francisella tularensis
•  
  Haemophilus ducreyi
•  
  Haemophilus influenzae
•  
  Klebsiella granulomatis
•  
  Klebsiella
  species
•  
  Neisseria gonorrhoeae
•  
  Shigella
  species
•  
  Vibrio cholerae
•  
  Yersinia pestis

•  
  Clostridium
  species
•  
  Fusobacterium fusiforme
•  
  Propionibacterium acnes

Rickettsiae

When available, the clinical microbiology laboratory should provide cumulative reports of

Quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (MICs). These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized test method (broth and/or agar).^1,2,4,6,7 The MIC values should be interpreted according to criteria provided in Table 1.

Quantitative methods that require measurement of zone diameters can also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. The zone size should be determined using a standardized test method .^1,3,4 This procedure uses paper disks impregnated with 30 mcg doxycycline to test the susceptibility of microorganisms to doxycycline. The disk diffusion interpretive criteria are provided in Table 1.

For anaerobic bacteria, the susceptibility to doxycycline can be determined by a standardized test method.^1,5 The MIC values obtained should be interpreted according to the criteria provided in Table 1

•  * Organisms susceptible to tetracycline are also considered susceptible to doxycycline. However, some organisms that are intermediate or resistant to tetracycline may be susceptible to doxycycline.
•  † The current absence of resistance isolates precludes defining any results other than "Susceptible". If isolates yielding MIC results other than susceptible, they should be submitted to a reference laboratory for further testing.
•  ‡ Gonococci with 30 mcg tetracycline disk zone diameters of less than 19 mm usually indicate a plasmid-mediated tetracycline resistant
  Neisseria gonorrhoeae
  isolate. Resistance in these strains should be confirmed by a dilution test (MIC ≥ 16 mcg per mL).

A report of

Standardized susceptibility test procedures require the use of laboratory controls to monitor and ensure the accuracy and precision of the supplies and reagents used in the assay, and the techniques of the individuals performing the test.^{1,2,3,4,5,6,7} Standard doxycycline and tetracycline powders should provide the following range of MIC values noted in Table 2. For the diffusion technique using the 30 mcg doxycycline disk or 30 mcg tetracycline disk, the criteria noted in

^*ATCC is the American Type Culture Collection