Reconstitution and Administration 
Tetracycline133 and tetracycline hydrochloride132 are administered orally. Although tetracycline hydrochloride has been administered by IM and IV injection, parenteral preparations of the drug are no longer commercially available in the US.
To reduce the risk of esophageal irritation and ulceration, tetracycline capsules or tablets should be administered with adequate amounts of fluid132,133 and probably should not be given at bedtime or to patients with esophageal obstruction or compression.
Because food and/or milk reduce GI absorption of tetracycline and tetracycline hydrochloride,91,96,132,133,146 oral preparations of the drugs should be given 1 hour before or 2 hours after meals and/or milk.
Dosage of tetracycline and tetracycline hydrochloride is expressed in terms of tetracycline hydrochloride.
The usual adult oral dosage of tetracycline hydrochloride is 1-2 g daily given in 2-4 divided doses.132,133 A dosage of 500 mg twice daily or 250 mg 4 times daily may be adequate for mild to moderate infections; a dosage of 500 mg 4 times daily may be required for severe infections.132,133
The usual oral dosage of tetracycline hydrochloride for children older than 8 years of age is 25-50 mg/kg daily given in 4 divided doses.132,133 The American Academy of Pediatrics (AAP) states that oral tetracycline is inappropriate for severe infections.114
For the adjunctive treatment of inflammatory acne, 500 mg to 1 g of tetracycline hydrochloride is given orally in 4 divided doses daily for 1-2 weeks or until clinical improvement occurs. Dosage is then decreased slowly to 125-500 mg daily or the lowest dosage which suppresses lesions. This dosage is then continued until clinical improvement allows discontinuation of the drug. Prolonged maintenance therapy may be necessary.
For information on the topical use of tetracyclines in acne, see Tetracyclines 84:04.04.
In severe cases of actinomycosis, the usual dosage of tetracycline hydrochloride has been given orally for 12-18 months after 3-4 weeks of penicillin G.
Although doxycycline generally is the tetracycline recommended for postexposure prophylaxis following suspected or confirmed exposure to aerosolized anthrax spores in the context of biologic warfare or bioterrorism, some experts state that in vitro studies suggest that adults can receive oral tetracycline hydrochloride in a dosage of 500 mg every 6 hours for postexposure prophylaxis following exposure to anthrax spores† if necessary as an alternative to doxycycline.122 Although the optimum duration of postexposure prophylaxis after an inhalation exposure to B. anthracis spores is unclear,140,123 prolonged postexposure prophylaxis is generally recommended because of the possible persistence of anthrax spores in lung tissue following aerosol exposure.122,125,123,127,123 A duration of 60 days may be adequate for a low-dose exposure, but a duration longer than 4 months may be necessary to reduce the risk following a high-dose exposure.140 The US Working Group on Civilian Biodefense and the US Army Medical Research Institute of Infectious Diseases (USAMRIID) recommend that postexposure prophylaxis be continued for at least 60 days in individuals who are not fully immunized against anthrax and when anthrax vaccine is unavailable or cannot be used for postexposure vaccination.122,123
Treatment of Inhalational Anthrax
Although doxycycline generally is the tetracycline recommended for treatment of inhalational anthrax, some experts state that in vitro studies suggest that adults can receive oral tetracycline hydrochloride in a dosage of 500 mg every 6 hours if necessary as an alternative to oral doxycycline.122,127
The US Centers for Disease Control and Prevention (CDC) and other experts (e.g., US Working Group on Civilian Biodefense, USAMRIID) recommend that treatment of inhalational anthrax be initiated with a multiple-drug regimen that includes ciprofloxacin or doxycycline and 1 or 2 other anti-infectives predicted to be effective.122,127 IV therapy with a multiple-drug parenteral regimen may not be possible if large numbers of individuals require treatment in a mass casualty setting; in these circumstances, some experts recommend that treatment with an oral regimen recommended for postexposure prophylaxis is an option.122,127 (See Anthrax under Dosage and Administration: Dosage in Doxycycline 8:12.24.)
For the treatment of balantidiasis† caused by Balantidium coli , the usual dosage of oral tetracycline hydrochloride is 500 mg 4 times daily for 10 days in adults112 and 40 mg/kg in 4 divided doses daily (up to 2 g daily) for 10 days in children 8 years of age or older.112,114
For the treatment of brucellosis, the manufacturers recommend that tetracycline hydrochloride be given in a dosage of 500 mg orally 4 times daily for 3 weeks in conjunction with IM streptomycin (1 g twice daily during the first week and once daily during the second week of treatment).132,133 The AAP recommends an oral tetracycline dosage of 30-40 mg/kg daily (up to 2 g daily) in 4 divided doses given for at least 6 weeks.114
A tetracycline (usually doxycycline) generally is used in conjunction with another anti-infective (e.g., streptomycin or gentamicin and/or rifampin) to reduce the likelihood of relapse, especially for severe infections and when there are complications such as meningitis, endocarditis, or osteomyelitis.114,123,145 Monotherapy is no longer recommended for the treatment of brucellosis since such therapy is associated with a high relapse rate.114,123,145
The usual duration of treatment of brucellosis is at least 4-6 weeks;114,123,145 streptomycin or gentamicin usually is given concomitantly for up to 2-3 weeks and/or rifampin is given for the full duration of treatment.114,123,145 More prolonged therapy may be required for complicated disease (e.g., hepatitis, splenitis, meningoencephalitis, endocarditis, osteomyelitis).123,145 Meningoencephalitis and endocarditis should be treated for at least 90 days and may require a treatment duration of 6 months or more.123
For the treatment of melioidosis† caused by Burkholderia pseudomallei , oral tetracycline has been given in a dosage of 2-3 g for 1-3 months. However, doxycycline is the preferred tetracycline for the treatment of melioidosis and other infections caused by Burkholderia .123,142 (See Burkholderia Infections under Dosage and Administration: Dosage in Doxycycline 8:12.24.)
If tetracycline hydrochloride is used in the treatment of Campylobacter fetus infections, some clinicians recommend that the usual dosage of the drug be given for 10 days.
When tetracycline hydrochloride is used as an alternative to the drugs of choice for the treatment of chancroid (genital ulcers caused by Haemophilus ducreyi ), some clinicians recommend that the usual oral dosage of the drug be given for 2-4 weeks.
Chlamydial and Mycoplasmal Infections
Uncomplicated Urethral, Endocervical, or Rectal Infections
For the treatment of uncomplicated urethral, endocervical, or rectal infections caused by Chlamydia trachomatis , the manufacturers and some clinicians suggest that adults can receive oral tetracycline hydrochloride in a dosage of 500 mg 4 times daily for at least 7 days.102,132,133 However, doxycycline is the tetracycline recommended by the CDC for the treatment of these urogenital infections, including presumptive treatment of chlamydial infections in patients with gonorrhea.101
Mycoplasma pneumoniae Infections
Atypical pneumonia caused by Mycoplasma pneumoniae has been treated with the usual oral dosage of tetracycline hydrochloride given for 1-4 weeks.
The CDC states that psittacosis (ornithosis) caused by Chlamydophila psittaci (formerly Chlamydia psittaci ) usually responds to oral tetracycline hydrochloride given in a dosage of 500 mg 4 times daily.100,104,114,132,133 Doxycycline and tetracycline are the drugs of choice.100,114 Although fever and symptoms usually are controlled within 48-72 hours, therapy should be continued for at least 10-14 days after defervescence to prevent relapse.100 For initial treatment of severely ill patients, an IV regimen of doxycycline hyclate may be indicated.100
Dientamoeba fragilis Infections
For the treatment of infections caused by Dientamoeba fragilis †, oral tetracycline hydrochloride is given in a dosage of 500 mg 4 times daily for 10 days in adults and 40 mg/kg in 4 divided doses daily (up to 2 g daily) for 10 days in children 8 years of age or older.112
Gonorrhea and Associated Infections
The manufacturers state that uncomplicated gonorrhea in adults may be treated with oral tetracycline hydrochloride in a dosage of 500 mg 4 times daily for 7 days.132,133 However, tetracyclines are not included in current CDC guidelines for the treatment of gonorrhea101 and doxycycline is the preferred tetracycline for presumptive treatment of coexisting chlamydial infections in patients being treated for gonococcal infections.101
For the treatment of acute, sexually transmitted epididymitis† caused by N. gonorrhoeae and/or C. trachomatis in adults and children 8 years of age and older, some clinicians suggest that oral tetracycline hydrochloride can be given in dosage of 500 mg 4 times daily for 10 days in conjunction with a single 250-mg IM dose of ceftriaxone.102 However, the CDC recommends oral doxycycline in conjunction with a single IM dose of ceftriaxone for treatment of these infections.101
Granuloma Inguinale (Donovanosis)
The usual oral dosage of tetracycline hydrochloride has been given for 2-4 weeks for the treatment of granuloma inguinale (donovanosis) caused by Klebsiella granulomatis (formerly Calymmatobacterium granulomatis ). However, doxycycline is the tetracycline recommended by the CDC for the treatment of donovanosis.101
Helicobacter pylori Infection and Duodenal Ulcer Disease
For the treatment of Helicobacter pylori (formerly Campylobacter pylori or C. pyloridis ) infection in adults with an active duodenal ulcer, the FDA-labeled dosage of tetracycline hydrochloride is 500 mg in combination with metronidazole (250 mg) and bismuth subsalicylate (525 mg) 4 times daily (at meals and at bedtime) for 14 days; these drugs should be given concomitantly with an H2-receptor antagonist in recommended dosage.110,134 Tetracycline hydrochloride (generally in a dosage of 500 mg 4 times daily) also has been used in other multiple-drug regimens† with at least 2 other agents that have activity against H. pylori .111,115,116,117,134 If an initial 14-day regimen does not eradicate H. pylori , a retreatment regimen that does not include metronidazole should be used.134
The minimum duration of therapy required to eradicate H. pylori infection in peptic ulcer disease has not been fully established.105,106,115,116 The ACG and many clinicians107,108 currently recommend 1 week of therapy with a proton-pump inhibitor and 2 anti-infective agents (usually clarithromycin and amoxicillin or metronidazole), or a 3-drug, bismuth-based regimen (e.g., bismuth-metronidazole-tetracycline) concomitantly with a proton-pump inhibitor, for treatment of H. pylori infection.107,108,119 However, the ACG states that in a cost-sensitive environment, an alternative regimen consisting of a bismuth salt, metronidazole, and tetracycline for 14 days is a reasonable choice in patients who are compliant and in whom there is a low expectation of metronidazole resistance (no prior exposure to the drug and a low regional prevalence of resistance).107 (See Helicobacter pylori Infection in Uses: GI Infections, in the Tetracyclines General Statement 8:12.24.)
When penicillin G was contraindicated or was ineffective for the treatment of leptospirosis†, tetracycline hydrochloride daily has been given for 5-7 days in a dosage of 1-2 g daily. Doxycycline is the preferred tetracycline for treatment or prevention of these infections.104,141
For the treatment of early Lyme disease†, an oral tetracycline hydrochloride dosage of 250-500 mg (preferably 500 mg in adults) 4 times daily for 10-30 days has been used in adults.109,118 However, the Infectious Diseases Society of America (IDSA) and other clinicians recommend doxycycline when a tetracycline is used in the treatment of Lyme disease.104,113,114,118,120,121 (See Lyme Disease in Uses: Spirochetal Infections, in the Tetracyclines General Statement 8:12.24 and see Lyme Disease under Dosage and Administration: Dosage in Doxycycline 8:12.24.)
Treatment of Uncomplicated Malaria
When oral tetracycline hydrochloride is used in conjunction with oral quinine sulfate for the treatment of uncomplicated chloroquine-resistant Plasmodium falciparum malaria†, the CDC and other clinicians recommend that adults receive 250 mg of tetracycline hydrochloride 4 times daily for 7 days given in conjunction with quinine sulfate (650 mg 3 times daily given for 3 days if malaria was acquired in Africa or South America or for 7 days if acquired in Southeast Asia).112,129 These experts recommend that children 8 years of age or older receive oral tetracycline hydrochloride in a dosage of 6.25 mg/kg 4 times daily for 7 days given in conjunction with oral quinine sulfate (10 mg/kg 3 times daily given for 3 days if infection was acquired in Africa or South America or for 7 days if acquired in Southeast Asia).112,129
When oral tetracycline hydrochloride is used in conjunction with quinine sulfate and primaquine phosphate for the treatment of uncomplicated chloroquine-resistant P. vivax malaria†, the CDC and other clinicians recommend that adults receive 250 mg of tetracycline hydrochloride 4 times daily for 7 days given in conjunction with oral quinine sulfate (650 mg 3 times daily given for 3 days if malaria was acquired in Africa or South America or for 7 days if acquired in Southeast Asia).129 These experts recommend that children 8 years of age or older receive tetracycline hydrochloride in a dosage of 6.25 mg/kg 4 times daily for 7 days given in conjunction with oral quinine sulfate (10 mg/kg 3 times daily given for 3 days if infection was acquired in Africa or South America or for 7 days if acquired in Southeast Asia).129 In addition, a 14-day regimen of oral primaquine (30 mg once daily in adults or 0.6 mg/kg once daily in children) should be given with the quinine sulfate and tetracycline hydrochloride regimen to provide a radical cure and prevent delayed attacks or relapse of P. vivax malaria.129
For additional information on treatment of uncomplicated malaria, see Uses: Malaria, in Quinine Sulfate 8:30.08.
When tetracycline hydrochloride is used in conjunction with IV quinidine gluconate (followed by oral quinine sulfate) for the treatment of severe malaria caused by P. falciparum †, adults who can tolerate oral therapy may receive 250 mg of tetracycline hydrochloride 4 times daily for 7 days.129 Children 8 years of age or older who can tolerate oral therapy may receive oral tetracycline hydrochloride in a dosage of 6.25 mg/kg 4 times daily for 7 days.129 Pediatric dosage should not exceed the recommended adult oral dosage.129 Patients intolerant of oral therapy may receive IV doxycycline hyclate or IV clindamycin for initial therapy in conjunction with IV quinidine gluconate until they can be switched to oral therapy.129
For additional information on treatment of severe malaria, see Uses: Malaria, in Quinidine 24:04.04.04.
If oral tetracycline hydrochloride is used for the treatment of plague caused by Yersinia pestis , adults should receive 2-4 g daily in 4 divided doses123,124,144 and children 8 years of age or older should receive 25-50 mg/kg daily in 4 divided doses.144
Prompt initiation of anti-infective therapy (within 18-24 hours of symptom onset) is essential in the treatment of pneumonic plague.123,124 Treatment of pneumonic plague should be initiated with a parenteral regimen (e.g., IV doxycycline, IM streptomycin, IM or IV gentamicin), although an oral regimen may be substituted when the patient's condition improves or if parenteral therapy is unavailable.123,124 Anti-infective therapy usually is continued for 10 days;124 some experts recommend a duration of at least 10-14 days.123
For postexposure prophylaxis following high-risk exposure to Y. pestis †, including exposure that occurs in the context of biologic warfare or bioterrorism, some experts recommend that adults receive tetracycline hydrochloride 1-2 g daily in 2 or 4 divided doses123,143,144 and children 8 years of age or older receive 25-50 mg/kg daily in 2 or 4 divided doses.143,144
The recommended duration of prophylaxis following exposure to plague aerosol or a patient with suspected pneumonic plague is 7 days123,124,143 or the duration of exposure risk plus 7 days.123 Some experts recommend that postexposure anti-infective prophylaxis be given to all asymptomatic individuals with exposure to plague aerosol and all asymptomatic individuals who have had household, hospital, or other close contact (within about 2 m) with an individual who has pneumonic plague; however, any exposed individual who develops a temperature of 38.5°C or higher or new cough should promptly receive a parenteral anti-infective for treatment of the disease.123,124
For the treatment of louse-borne relapsing fever caused by Borrelia recurrentis , the usual oral dosage of tetracycline hydrochloride has been given until the patient is afebrile for 7 days. A single 500-mg oral dose of the drug has also been effective in some patients.
For the treatment of Rocky Mountain spotted fever, louse-borne (epidemic) typhus, Brill-Zinsser disease, endemic (murine) typhus, Q fever, and rickettsialpox, the usual adult dosage of oral tetracycline hydrochloride generally is given for at least 3-7 days or until the patient has been afebrile for approximately 2-3 days. Doxycycline is the drug of choice for most rickettsial infections.114
For the treatment of acute Q fever caused by Coxiella burnetii , some clinicians recommend that oral tetracycline hydrochloride be given in a dosage of 500 mg every 6 hours for at least 14 days.123
It has been suggested that tetracycline hydrochloride given in a dosage of 500 mg every 6 hours for 5-7 days may be effective as prophylaxis against Q fever† and may prevent clinical disease if initiated 8-12 days after exposure; however, such prophylaxis is not effective and may only prolong the onset of disease if given immediately (1-7 days) after exposure.123
While parenteral penicillin G is the drug of choice for all stages of syphilis, the CDC and AAP state that nonpregnant adults or adolescents with primary or secondary syphilis who are hypersensitive to penicillin can receive 500 mg of oral tetracycline hydrochloride 4 times daily for 14 days.101,114 In addition, nonpregnant adults or adolescents with early latent syphilis (syphilis of less than 1-year duration) who are hypersensitive to penicillin can receive 500 mg of oral tetracycline hydrochloride 4 times daily for 14 days and those with late latent syphilis, latent syphilis of unknown duration, or tertiary syphilis (except neurosyphilis) can receive 500 mg 4 times daily for 28 days.101,114 For the treatment of syphilis, some manufacturers state that a total of 30-40 g should be given in equally divided doses over a period of 10-15 days.132,133
Care should be taken to encourage optimal compliance with these regimens, since patient compliance with multiple-day tetracycline regimens may be poor.101,114 If compliance with the tetracycline regimen and serologic follow-up cannot be ensured, patients with a history of penicillin hypersensitivity should be desensitized and treated with penicillin G.101 The CDC states that infants and children with syphilis who are hypersensitive to penicillin should be desensitized, if necessary, and treated with penicillin.101 For information on recommendations regarding treatment and follow-up for all stages and forms of syphilis, see Spirochetal Infections: Syphilis, under Uses in the Natural Penicillins General Statement 8:12.16.04.
If tetracycline hydrochloride is used for the treatment of tularemia that occurs as the result of exposure to Francisella tularensis in the context of biologic warfare or bioterrorism or naturally occurring or endemic tularemia, some experts recommend that adults receive 500 mg orally 4 times daily123 for at least 14-21 days.123,135 Relapse may occur as long as 6 months after treatment with tetracycline; however, retreatment with the same dosage usually is curative.
If tetracycline hydrochloride is used for postexposure prophylaxis following a high-risk laboratory exposure to F. tularensis (e.g., spill, centrifuge accident, needlestick injury) or in individuals exposed to the organism in the context of biologic warfare or bioterrorism, some experts (e.g., USAMRIID) state that adults can receive 500 mg orally 4 times daily.123 Postexposure prophylaxis should be initiated within 24 hours of exposure and continued for at least 14 days.123,135
Postexposure prophylaxis usually is not recommended after exposure to natural or endemic tularemia (e.g., tick bite, rabbit or other animal exposure) and is unnecessary in close contacts of tularemia patients since human-to-human transmission does not occur.123
For the treatment of cholera in conjunction with fluid and electrolyte replacement, some clinicians recommend a tetracycline hydrochloride dosage of 500 mg 4 times daily for 3 days.103
When penicillin G was contraindicated or was ineffective,104 1-2 g of tetracycline hydrochloride daily has been given for 10-14 days for the treatment of yaws caused by Treponema pertenue 104,132,133 or the treatment of pinta caused by T. carateum . Doxycycline is the preferred tetracycline for treatment or prevention of these spirochetal infections.141
Pleural and Pericardial Effusions
When used as a sclerosing agent to control pleural effusions† caused by metastatic tumors, 500 mg of tetracycline hydrochloride (a parenteral formulation of tetracycline hydrochloride no longer is commercially available in the US) has been diluted with 30-50 mL of 0.9% sodium chloride injection and instilled into the chest through a thoracostomy tube followed by instillation of 50 mL of 0.9% sodium chloride injection.
To control pericardial effusions† caused by metastatic tumors, 500 mg to 1 g of tetracycline hydrochloride has been diluted with 20 mL of 0.9% sodium chloride injection and instilled intrapericardially through an indwelling pericardial cannula.
If tetracycline is used in patients with impaired renal function, doses and/or frequency of administration must be modified in response to the degree of renal impairment.132