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  • CLASSES

    Natural and Semi-Synthetic Tetracycline Antibiotics

    DEA CLASS

    Rx

    DESCRIPTION

    Semisynthetic tetracycline agent produced from chlortetracycline; wide spectrum of activity vs. gram-negative and gram-positive organisms; inactive against viruses and fungi.

    COMMON BRAND NAMES

    Emtet-500, Panmycin, Sumycin

    HOW SUPPLIED

    Emtet-500/Panmycin/Sumycin/Tetracycline/Tetracycline Hydrochloride Oral Cap: 250mg, 500mg

    DOSAGE & INDICATIONS

    For the treatment of necrotizing ulcerative gingivitis (Fusospirochetosis or Vincent's infection) and listeriosis (Listeria monocytogenes) when penicillin is contraindicated.
    Oral dosage
    Adults

    500 mg PO twice daily or 250 mg PO every 6 hours for mild to moderate infections. For severe infections, 500 mg PO every 6 hours may be necessary.

    Children and Adolescents 9 to 17 years

    25 to 50 mg/kg/day PO in 4 divided doses (Max: 500 mg/dose).

    For the treatment of actinomycosis caused by Actinomyces israelii when penicillin is contraindicated.
    Oral dosage
    Adults

    500 mg PO twice daily or 250 mg PO every 6 hours for mild to moderate infections. For severe infections, 500 mg PO every 6 hours may be necessary.

    Children and Adolescents 9 to 17 years

    25 to 50 mg/kg/day PO in 4 divided doses (Max: 500 mg/dose).

    For the treatment of yaws when penicillin is contraindicated.
    Oral dosage
    Adults

    500 mg PO twice daily or 250 mg PO every 6 hours for mild to moderate infections. For severe infections, 500 mg PO every 6 hours may be necessary.

    Children and Adolescents 9 to 17 years

    25 to 50 mg/kg/day PO in 4 divided doses (Max: 500 mg/dose).

    For the treatment of syphilis when penicillin is contraindicated.
    For primary, secondary, or early latent syphilis (caused by Treponema pallidum) in nonpregnant, penicillin-allergic patients.
    Oral dosage
    Adults

    500 mg PO every 6 hours for 14 days. If follow-up/compliance unsure, desensitize patient and treat with penicillin.

    Children and Adolescents 9 to 17 years

    25 to 50 mg/kg/day PO in 4 divided doses (Max: 500 mg/dose).

    For late latent syphilis in nonpregnant, penicillin-allergic patients.
    Oral dosage
    Adults

    500 mg PO every 6 hours for 4 weeks. If follow-up/compliance unsure, desensitize patient and treat with penicillin.

    Children and Adolescents 9 to 17 years

    25 to 50 mg/kg/day PO in 4 divided doses (Max: 500 mg/dose).

    For the treatment of uncomplicated gonorrhea.
    Oral dosage
    Adults

    Not recommended by guidelines. 500 mg PO 4 times daily for 7 days.

    Children and Adolescents 9 to 17 years

    Not recommended by guidelines. 25 to 50 mg/kg/day PO in 4 divided doses (Max: 500 mg/dose).

    For the treatment of chlamydia infection due to C. trachomatis, including urethritis, cervicitis, proctitis, chlamydial conjunctivitis, trachoma, and lymphogranuloma venereum.
    For the treatment of urethral, endocervical, or rectal infections due to C. trachomatis.
    Oral dosage
    Adults

    CDC does not recommend tetracycline for chlamydia. 500 mg PO 4 times daily for at least 7 days.

    Children 9 years and older and Adolescents

    CDC does not recommend tetracycline for chlamydia. 25 to 50 mg/kg/day PO in 4 divided doses (Max: 500 mg/dose).

    For the treatment of granuloma inguinale (Donovanosis) caused by Klebsiella granulomatis.
    Oral dosage
    Adults

    CDC does not include tetracycline in clinical practice guidelines.[59799] 500 mg PO twice daily or 250 mg PO every 6 hours for mild to moderate infections is the FDA-approved dosage. For severe infections, 500 mg PO every 6 hours may be necessary.[28392]

    Children and Adolescents 9 to 17 years

    CDC does not include tetracycline in clinical practice guidelines. 25 to 50 mg/kg/day PO in 4 divided doses (Max: 500 mg/dose) is the FDA-approved dosage.

    For the treatment of chancroid caused by Haemophilus ducreyi.
    Oral dosage
    Adults

    CDC does not include tetracycline in guidelines. 500 mg PO twice daily or 250 mg PO every 6 hours for mild to moderate infections is the FDA-approved dosage. For severe infections, 500 mg PO every 6 hours may be necessary.

    Children and Adolescents 9 to 17 years

    CDC does not include tetracycline in guidelines. 25 to 50 mg/kg/day PO in 4 divided doses (Max: 500 mg/dose) is the FDA-approved dosage.

    For the treatment of psittacosis.
    Oral dosage
    Adults

    500 mg PO twice daily or 250 mg PO every 6 hours for mild to moderate infections. For severe infections, 500 mg PO every 6 hours may be necessary.

    Children and Adolescents 9 to 17 years

    25 to 50 mg/kg/day PO in 4 divided doses (Max: 500 mg/dose).

    For the treatment of relapsing fever due to Borrelia recurrentis.
    Oral dosage
    Adults

    500 mg PO twice daily or 250 mg PO every 6 hours for mild to moderate infections. For severe infections, 500 mg PO every 6 hours may be necessary.

    Children and Adolescents 9 to 17 years

    25 to 50 mg/kg/day PO in 4 divided doses (Max: 500 mg/dose).

    For the treatment of tularemia caused by Francisella tularensi.
    Oral dosage
    Adults

    500 mg PO twice daily or 250 mg PO every 6 hours for mild to moderate infections. For severe infections, 500 mg PO every 6 hours may be necessary.

    Children and Adolescents 9 to 17 years

    25 to 50 mg/kg/day PO in 4 divided doses (Max: 500 mg/dose).

    For the treatment anthrax infection caused by susceptible strains of Bacillus anthracis when penicillin is contraindicated.
    Oral dosage
    Adults

    Guidelines do not recommend the use of tetracycline. For severe infections, 500 mg PO every 6 hours is the FDA-approved dosage.

    Children and Adolescents 9 to 17 years

    Guidelines do not recommend the use of tetracycline. 25 to 50 mg/kg/day PO in 4 divided doses (Max: 500 mg/dose) is the FDA-approved dosage.

    For the treatment of upper respiratory tract infections.
    Oral dosage
    Adults

    500 mg PO twice daily or 250 mg PO every 6 hours for mild to moderate infections. For severe infections, 500 mg PO every 6 hours may be necessary. Treat streptococcal infections for 10 days.

    Children and Adolescents 9 to 17 years

    25 to 50 mg/kg/day PO in 4 divided doses (Max: 500 mg/dose). Treat streptococcal infections for 10 days.

    For the treatment of lower respiratory tract infections.
    Oral dosage
    Adults

    500 mg PO twice daily or 250 mg PO every 6 hours for mild to moderate infections. For severe infections, 500 mg PO every 6 hours may be necessary.

    Children and Adolescents 9 to 17 years

    25 to 50 mg/kg/day PO in 4 divided doses (Max: 500 mg/dose).

    For the treatment of skin and skin structure infections.
    NOTE: Tetracyclines are not the drugs of choice in the treatment of any type of staphylococcal infection.
    Oral dosage
    Adults

    500 mg PO twice daily or 250 mg PO every 6 hours for mild to moderate infections. For severe infections, 500 mg PO every 6 hours may be necessary. Treat streptococcal infections for 10 days.

    Children and Adolescents 9 to 17 years

    25 to 50 mg/kg/day PO in 4 divided doses (Max: 500 mg/dose). Treat streptococcal infections for 10 days.

    For the treatment of bacterial urinary tract infection (UTI).
    Oral dosage
    Adults

    500 mg PO twice daily or 250 mg PO every 6 hours for mild to moderate infections. For severe infections, 500 mg PO every 6 hours may be necessary.

    Children and Adolescents 9 to 17 years

    25 to 50 mg/kg/day PO in 4 divided doses (Max: 500 mg/dose).

    For the treatment of shigellosis.
    Oral dosage
    Adults

    Guidelines recommend against the use of tetracycline. 500 mg PO twice daily or 250 mg PO every 6 hours for mild to moderate infections is the FDA-approved dosage. For severe infections, 500 mg PO every 6 hours may be necessary.

    Children and Adolescents 9 to 17 years

    Guidelines recommend against the use of tetracycline. 25 to 50 mg/kg/day PO in 4 divided doses (Max: 500 mg/dose) is the FDA-approved dosage.

    For the treatment of intestinal amebiasis caused by Entamoeba histolytica as adjunctive therapy.
    Oral dosage
    Adults

    500 mg PO twice daily or 250 mg PO every 6 hours for mild to moderate infections. For severe infections, 500 mg PO every 6 hours may be necessary.

    Children and Adolescents 9 to 17 years

    25 to 50 mg/kg/day PO in 4 divided doses (Max: 500 mg/dose).

    For the treatment of moderate to severe acne vulgaris as adjunctive therapy.
    Oral dosage
    Adults

    1 g/day PO in divided doses, then decrease slowly to 125 to 500 mg PO daily or every other day.

    Children and Adolescents 9 to 17 years

    1 g/day PO in divided doses, then decrease slowly to 125 to 500 mg PO daily or every other day.

    For the treatment of Rocky Mountain spotted fever, Q fever, murine typhus, Rickettsial pox, and tick-bite fever caused by Rickettsia sp..
    Oral dosage
    Adults

    500 mg PO twice daily or 250 mg PO every 6 hours for mild to moderate infections. For severe infections, 500 mg PO every 6 hours may be necessary. Doxycycline is the drug of choice for rickettsial diseases.

    Children and Adolescents 9 to 17 years

    25 to 50 mg/kg/day PO in 4 divided doses (Max: 500 mg/dose). Doxycycline is the drug of choice for rickettsial diseases.

    For the treatment of bartonellosis due to Bartonella bacilliformis.
    Oral dosage
    Adults

    500 mg PO twice daily or 250 mg PO every 6 hours for mild to moderate infections. For severe infections, 500 mg PO every 6 hours may be necessary.

    Children and Adolescents 9 to 17 years

    25 to 50 mg/kg/day PO in 4 divided doses (Max: 500 mg/dose).

    For the treatment of brucellosis caused by Brucella sp. in combination with streptomycin.
    Oral dosage
    Adults

    500 mg PO every 6 hours for 3 weeks in combination with streptomycin 1 g IM twice daily for the first week, then streptomycin 1 g IM once daily for the second week.

    Children and Adolescents 9 to 17 years

    25 to 50 mg/kg/day PO in 4 divided doses (Max: 500 mg/dose) for 3 weeks in combination with streptomycin.

    For the treatment of plague in a mass casualty setting following exposure to Yersinia pestis.
    NOTE: Doxycycline is the treatment of choice for plague in the mass casualty setting. Tetracycline should not be used in pregnant women.
    Oral dosage
    Adults

    1 g PO every 6 hours for 10 days. If antibiotic susceptibility testing allows, oral doxycycline, ciprofloxacin, or chloramphenicol could be used as alternatives.

    Children and Adolescents 9 to 17 years

    5 mg/kg/dose PO every 6 hours for 10 days (Max: 1 g/dose). If antibiotic susceptibility testing allows, oral doxycycline, ciprofloxacin, or chloramphenicol could be used as an alternative.[26696]

    For the treatment of cholera.
    Oral dosage
    Adults

    Guidelines recommend 500 mg PO every 6 hours for 3 days in conjunction with fluid and electrolyte replacement. The FDA-approved dosage is 500 mg PO twice daily or 250 mg PO every 6 hours for mild to moderate infections. For severe infections, 500 mg PO every 6 hours may be necessary.

    Children and Adolescents 9 to 17 years

    Guidelines recommend 12.5 mg/kg PO every 6 hours for 3 days (Max: 500 mg/dose) in conjunction with fluid and electrolyte replacement. The FDA-approved dosage is 25 to 50 mg/kg/day PO in 4 divided doses (Max: 500 mg/dose).

    For the treatment of acne rosacea†.
    Oral dosage
    Adults

    250 to 1,500 mg/day PO.

    Adolescents

    250 to 1,500 mg/day PO.

    For plague prophylaxis† following exposure to Yersinia pestis.
    NOTE: Doxycycline is the treatment of choice for plague prophylaxis. Tetracycline should not be used in pregnant women.
    Oral dosage
    Adults

    1 g PO every 6 hours for 7 days. If antibiotic susceptibility testing allows, oral doxycycline, ciprofloxacin, or chloramphenicol could be used as alternatives.

    Children and Adolescents 9 to 17 years

    5 mg/kg/dose PO every 6 hours for 7 days (Max: 1 g/dose). If antibiotic susceptibility testing allows, oral doxycycline, ciprofloxacin, or chloramphenicol could be used as alternatives.

    For the treatment of acute dental infection†, dentoalveolar infection†, or endodontic infection† including periodontitis† in combination with conventional treatment (e.g., scaling and root planing).
    For aggressive periodontitis (juvenile periodontitis)†.
    Oral dosage
    Children and Adolescents 9 to 17 years

    25 to 50 mg/kg/day PO divided in equal doses given twice daily for 14 to 21 days.

    For adjunct treatment to scaling and root planing for reduction of pocket depth and bleeding in patients with adult chronic periodontitis†.
    Oral dosage
    Adults

    250 mg PO every 6 hours for 14 to 21 days.

    For Helicobacter pylori (H. pylori) eradication†.
    Oral dosage
    Adults

    500 mg PO 4 times daily in combination with bismuth subsalicylate, metronidazole, and a proton pump inhibitor for 10 to 14 days is recommended as a first-line treatment option, particularly in patients with any previous macrolide exposure or a penicillin allergy. Bismuth quadruple therapy for 14 days is also recommended as a salvage regimen, particularly in patients failing clarithromycin triple therapy. A subsequent repeat course of bismuth quadruple therapy may be considered after failed prior bismuth quadruple therapy.

    Children and Adolescents 9 to 17 years

    Tetracycline is recommended in guidelines as part of bismuth-based quadruple therapy (bismuth subsalicylate, metronidazole, tetracycline, and proton pump inhibitor for 14 days); however, dosing is not provided. 25 to 50 mg/kg/day PO in 4 divided doses (Max: 500 mg/dose) is the FDA-approved dosage for other indications. Bismuth-based quadruple therapy is a first-line treatment option for patients infected with H. pylori strains with dual resistance to clarithromycin and metronidazole or strains with unknown susceptibility. Bismuth-based quadruple therapy may also be used in penicillin-allergic patients infected with H. pylori strains resistant to clarithromycin.

    For the treatment of uncomplicated malaria† due to P. falciparum or P. vivax.
    Oral dosage
    Adults

    250 mg PO 4 times daily for 7 days. Give in combination with quinine sulfate for P. falciparum or in combination with primaquine phosphate or tafenoquine for P. vivax.

    Children and Adolescents 8 to 17 years

    25 mg/kg/day PO divided 4 times daily (Max: 250 mg/dose) for 7 days. Give in combination with quinine sulfate for P. falciparum or in combination with primaquine phosphate or tafenoquine (16 years and older) for P. vivax.

    Children younger 1 to 7 years

    25 mg/kg/day PO divided 4 times daily (Max: 250 mg/dose) for 7 days. Give in combination with quinine sulfate for P. falciparum or in combination with primaquine phosphate for P. vivax. In rare instances, tetracycline may be used in children younger than 8 years if other options are not available or are not tolerated and benefit of use outweighs risks.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    2 g/day PO is suggested by the manufacturer; 4 g/day PO has been recommended in some clinical practice guidelines.

    Geriatric

    2 g/day PO is suggested by the manufacturer; 4 g/day PO has been recommended in some clinical practice guidelines.

    Adolescents

    50 mg/kg/day PO up to 2 g/day PO.

    Children

    9 years and older: 50 mg/kg/day PO up to 2 g/day PO.
    8 years or less: Safety and efficacy have not been established.

    Infants

    Safety and efficacy have not been established.

    Neonates

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Dose adjustment of tetracycline may be required in patients with hepatic impairment due to potential for reduced excretion and a prolonged half-life.

    Renal Impairment

    CrCl more than 90 mL/minute: no dosage adjustment needed.
    CrCl 51 to 90 mL/minute: extend dosing interval to every 8 to 12 hours.
    CrCl 10 to 50 mL/minute: extend dosing interval to every 12 to 24 hours.
    CrCl less than 10 mL/minute: extend dosing interval to every 24 hours.

    ADMINISTRATION

    Oral Administration

    Food and/or milk interferes with absorption of tetracycline. Administer on an empty stomach (i.e., at least one hour prior to or two hours after a meal and/or milk) with plenty of fluids.
    Administer with sufficient amounts of water to reduce the risk of esophageal irritation or ulceration.
    Divalent and trivalent cations significantly affect tetracycline absorption. Do not administer sucralfate (contains aluminum), oral iron supplements, or aluminum-, magnesium- or calcium-containing antacids in conjunction with oral tetracycline. Multivitamins containing manganese or zinc salts will also decrease absorption of tetracycline.
    To reduce the risk of esophageal irritation or ulceration, do not be administer at bedtime or to patients with esophageal obstruction or compression.

    Topical Administration

    Reconstitution of powder for topical solution: Insert plastic applicator unit containing the powder into the bottle containing the diluent. By pressing firmly on the center of the applicator top, release powder into the liquid.
    Apply solution by tilting bottle and rubbing the applicator top over the skin while gently applying pressure. Flow rate is determined by increasing or decreasing pressure on the skin. Apply generously until skin is thoroughly wet.

    Ophthalmic Administration

    Apply topically to the eye taking care to avoid contamination. For ophthalmic use only.
    Instruct patient on proper instillation of eye ointment or solution (see Patient Information).
    Do not to touch the tip of the dropper or tube to the eye, fingertips, or other surface.
    The ointment may be applied at night in combination with daytime use of the solution or before application of an eye patch.

    Other Administration Route(s)

    Periodontal Administration (Actisite Periodontal Fibers)
    Fibers should be in contact with the base of the pocket and should be filled in to closely approximate the anatomy of the pocket.
    An appropriate cyanocrylate adhesive should be used to secure the fiber in place.
    If fibers are lost before 7 days after insertion, fibers should be replaced.
    Instruct patient on actions to avoid or prevent dislodging fibers.

    STORAGE

    Emtet-500:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Panmycin:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Sumycin:
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    Sulfite hypersensitivity, tartrazine dye hypersensitivity, tetracyclines hypersensitivity

    Tetracycline is contraindicated in patients with known tetracyclines hypersensitivity. Topical tetracycline preparations contain sodium sulfites. Oral dosage forms may contain tartrazine dye. These preparations should be used with caution in patients with a known sulfite hypersensitivity or tartrazine dye hypersensitivity. Sensitivity reactions are more common in asthmatic than in non-asthmatic patients.

    Pregnancy

    Tetracycline is classified as FDA pregnancy category D. All tetracyclines have a detrimental effect on the skeletal development and bone growth of the fetus or child. Do not use tetracycline in the second half of pregnancy unless benefits from treatment outweigh the risks to the fetus; use with extreme caution. In a nested, case-control study (n = 87,020 controls; 8,702 cases) within the Quebec Pregnancy Cohort, tetracycline use during early pregnancy was associated with an increased risk of spontaneous abortion (adjusted odds ratio (aOR) 2.59, 95% CI: 1.97 to 3.41, 67 exposed cases); residual confounding by severity of infection may be a potential limitation of this study. Guidelines suggest tetracycline may be used for the treatment of uncomplicated malaria during pregnancy in rare instances if other options are not available or are not tolerated and benefit of use outweighs risks.

    Children, infants, neonates

    Tetracyclines may have a serious effect on the bones and teeth in young children. Tetracyclines are incorporated into bones and teeth that are undergoing calcification. This may cause permanent yellow or brown discoloration and enamel hypoplasia in developing teeth. Do not use tetracycline in neonates, infants, and children younger than 8 years, except for anthrax, unless other drugs are not likely to be effective or are contraindicated. Guidelines suggest tetracycline may be used for the treatment of uncomplicated malaria in children younger than 8 years in rare instances if other options are not available or are not tolerated and benefit of use outweighs risks.

    Breast-feeding

    Tetracyclines are distributed in small amounts into breast milk. In general, manufacturers recommend that tetracycline antibiotics not be used in breast feeding mothers due to a theoretical risk of causing teeth discoloration, enamel hypoplasia, inhibition of linear skeletal growth, oral and vaginal thrush, or photosensitivity reactions in the nursing infant. However, because tetracyclines bind to calcium in the maternal breast milk, the risk for oral absorption by the infant is minimal. The American Academy of Pediatrics considers tetracycline to be compatible with breast-feeding. Data are available regarding milk concentrations and infant serum concentrations following tetracycline use in breast-feeding women. In a study using a microbiologic assay, milk tetracycline concentrations were measured in an unspecified number of nursing mothers at 9 am after various dosages of tetracycline during the previous days. Whether the women had mastitis and the time postpartum were not stated. Milk levels were reported as 2.5 mg/L after a daily dose of 1 gram orally for 3 days, to 2 mg/L after a daily dose of 1.5 grams orally for 2 days, and to 2.5 mg/L after a daily dose of 2 grams orally for 3 days. In these women, no adverse effects were noted in an unspecified number of their breast-fed infants; the ages of the infants and extent of breast-feeding were also not stated. In another study, 5 women were given oral tetracycline (500 mg 4 times a day for 3 days); milk levels ranged from 0.43 to 2.58 mg/L (times not specified). Their infants were allowed to nurse and the infants' tetracycline concentrations were undetectable (< 50 mcg/L) in serum and no adverse effects were observed. Finally, in an observational study of 251 women, 23.8% of nursing mothers received tetracycline during breast-feeding; no gross adverse effect occurred in any of the breast-fed infants. Studies of long-term tetracycline use in breast-feeding are lacking. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    Renal disease, renal failure, renal impairment

    If renal impairment exists, even usual oral or parenteral doses may lead to excessive systemic accumulation of tetracycline. High serum levels of the tetracyclines may lead to azotemia, hyperphosphatemia, or metabolic acidosis. Under such conditions, monitoring of creatinine and BUN is recommended, and dosage adjustments are necessary in patients with renal disease, including renal failure.

    Hepatic disease

    Dose adjustment may be required in patients with hepatic disease because hepatic excretion of tetracycline into bile can be delayed in these patients.

    Sunlight (UV) exposure

    Photosensitivity is a risk of tetracycline therapy and can occur when patients treated with tetracycline are exposed to sunlight (UV) exposure. Tetracycline should be discontinued at the first sign of erythema. Photosensitivity reactions are believed to be due to accumulation of the drug in the skin and are mostly phototoxic in nature, but photoallergic reactions also can occur. Reactions can develop from within a few minutes to up to several hours after exposure and will last for 1—2 days after discontinuation of the drug. It is generally agreed that sunscreens provide limited protection for this reaction. Direct sunlight (UV) exposure should be avoided or minimized.

    Surgery

    In patients undergoing surgery with methoxyflurane anesthesia, concurrent use of tetracycline can increase the risk of nephrotoxicity (sometimes fatal).

    Corticosteroid therapy

    Ophthalmic tetracycline and ophthalmic corticosteroid therapy are not recommended for combination therapy. Combination therapy may mask the clinical signs of bacterial, viral, or fungal infections. Corticosteroids may suppress hypersensitivity reactions to tetracycline therapy.

    Colitis, diarrhea, GI disease, inflammatory bowel disease, pseudomembranous colitis, ulcerative colitis

    Almost all antibacterial agents like tetracycline have been associated with pseudomembranous colitis (antibiotic-associated colitis) which may range in severity from mild to life-threatening. In the colon, overgrowth of Clostridia may exist when normal flora is altered subsequent to antibacterial administration. The toxin produced by Clostridium difficile is a primary cause of pseudomembranous colitis. It is known that systemic use of antibiotics predisposes patients to development of pseudomembranous colitis. Consideration should be given to the diagnosis of pseudomembranous colitis in patients presenting with diarrhea following antibacterial administration. Systemic antibiotics should be prescribed with caution to patients with inflammatory bowel disease such as ulcerative colitis or other GI disease. If diarrhea develops during therapy, the drug should be discontinued. Following diagnosis of pseudomembranous colitis, therapeutic measures should be instituted. In milder cases, the colitis may respond to discontinuation of the offending agent. In moderate to severe cases, fluids and electrolytes, protein supplementation, and treatment with an antibacterial effective against Clostridium difficile may be warranted. Products inhibiting peristalsis are contraindicated in this clinical situation. Practitioners should be aware that antibiotic-associated colitis has been observed to occur over two months or more following discontinuation of systemic antibiotic therapy; a careful medical history should be taken.

    Sexually transmitted disease

    While tetracycline may be used to treat certain sexually transmitted diseases (STD), the drug may mask or delay the symptoms of incubating syphilis when given as part of an STD treatment regimen. All patients with a diagnosed or suspected STD should be tested for other STDs, which may include HIV, syphilis, chlamydia, and gonorrhea, at the time of diagnosis. Initiate appropriate therapy and perform follow-up testing as recommended based upon sexually transmitted disease diagnosis.

    Geriatric

    In general, dose selection of tetracycline for a geriatric patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents (e.g., geriatric adults) of long-term care facilities. According to OBRA, use of antibiotics should be limited to confirmed or suspected bacterial infections. Antibiotics are non-selective and may result in the eradication of beneficial microorganisms while promoting the emergence of undesired ones, causing secondary infections such as oral thrush, colitis, or vaginitis. Any antibiotic may cause diarrhea, nausea, vomiting, anorexia, and hypersensitivity reactions.

    Laboratory test interference

    Administration of tetracycline may result in laboratory test interference. Antimicrobials are known to suppress H. pylori; thus, ingestion of these agents within 4 weeks of performing diagnostic tests for H. pylori may lead to false negative results. At a minimum, instruct the patient to avoid the use of tetracycline in the 4 weeks prior to the test.

    ADVERSE REACTIONS

    Severe

    exfoliative dermatitis / Delayed / 0-1.0
    increased intracranial pressure / Early / Incidence not known
    papilledema / Delayed / Incidence not known
    enterocolitis / Delayed / Incidence not known
    esophageal ulceration / Delayed / Incidence not known
    hepatic failure / Delayed / Incidence not known
    serum sickness / Delayed / Incidence not known
    pericarditis / Delayed / Incidence not known
    angioedema / Rapid / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    lupus-like symptoms / Delayed / Incidence not known
    teratogenesis / Delayed / Incidence not known
    hemolytic anemia / Delayed / Incidence not known
    thrombotic thrombocytopenic purpura (TTP) / Delayed / Incidence not known
    azotemia / Delayed / Incidence not known

    Moderate

    pseudotumor cerebri / Delayed / Incidence not known
    blurred vision / Early / Incidence not known
    esophagitis / Delayed / Incidence not known
    dysphagia / Delayed / Incidence not known
    glossitis / Early / Incidence not known
    candidiasis / Delayed / Incidence not known
    superinfection / Delayed / Incidence not known
    erythema / Early / Incidence not known
    enamel hypoplasia / Delayed / Incidence not known
    thrombocytopenia / Delayed / Incidence not known
    eosinophilia / Delayed / Incidence not known
    neutropenia / Delayed / Incidence not known

    Mild

    nail discoloration / Delayed / 0-1.0
    diplopia / Early / Incidence not known
    headache / Early / Incidence not known
    vomiting / Early / Incidence not known
    anorexia / Delayed / Incidence not known
    tongue discoloration / Delayed / Incidence not known
    diarrhea / Early / Incidence not known
    nausea / Early / Incidence not known
    purpura / Delayed / Incidence not known
    fever / Early / Incidence not known
    maculopapular rash / Early / Incidence not known
    arthralgia / Delayed / Incidence not known
    urticaria / Rapid / Incidence not known
    photosensitivity / Delayed / Incidence not known
    rash / Early / Incidence not known
    tooth discoloration / Delayed / Incidence not known
    Jarisch-Herxheimer reaction / Early / Incidence not known

    DRUG INTERACTIONS

    Acitretin: (Contraindicated) The concomitant use of acitretin and systemic tetracyclines is contraindicated, due to the potential for increased cranial pressure and an increased risk of pseudotumor cerebri (benign intracranial hypertension). Pseudotumor cerebri has been reported with systemic retinoid use alone and early signs and symptoms include papilledema, headache, nausea, vomiting and visual disturbances.
    Aluminum Hydroxide: (Moderate) Separate administration of tetracycline and antacids by 2 to 3 hours. Coadministration may impair absorption of tetracycline which may decrease its efficacy.
    Aluminum Hydroxide; Magnesium Carbonate: (Moderate) Separate administration of tetracycline and antacids by 2 to 3 hours. Coadministration may impair absorption of tetracycline which may decrease its efficacy.
    Aluminum Hydroxide; Magnesium Hydroxide: (Moderate) Separate administration of tetracycline and antacids by 2 to 3 hours. Coadministration may impair absorption of tetracycline which may decrease its efficacy.
    Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Moderate) Separate administration of tetracycline and antacids by 2 to 3 hours. Coadministration may impair absorption of tetracycline which may decrease its efficacy.
    Aluminum Hydroxide; Magnesium Trisilicate: (Moderate) Separate administration of tetracycline and antacids by 2 to 3 hours. Coadministration may impair absorption of tetracycline which may decrease its efficacy.
    Amoxicillin: (Major) Avoid the coadministration of tetracycline antibiotics with penicillins as tetracyclines may interfere with the bactericidal action of penicillins.
    Amoxicillin; Clarithromycin; Lansoprazole: (Major) Avoid the coadministration of tetracycline antibiotics with penicillins as tetracyclines may interfere with the bactericidal action of penicillins.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Avoid the coadministration of tetracycline antibiotics with penicillins as tetracyclines may interfere with the bactericidal action of penicillins.
    Amoxicillin; Clavulanic Acid: (Major) Avoid the coadministration of tetracycline antibiotics with penicillins as tetracyclines may interfere with the bactericidal action of penicillins.
    Ampicillin: (Major) Avoid the coadministration of tetracycline antibiotics with penicillins as tetracyclines may interfere with the bactericidal action of penicillins.
    Ampicillin; Sulbactam: (Major) Avoid the coadministration of tetracycline antibiotics with penicillins as tetracyclines may interfere with the bactericidal action of penicillins.
    Antacids: (Moderate) Separate administration of tetracycline and antacids by 2 to 3 hours. Coadministration may impair absorption of tetracycline which may decrease its efficacy.
    Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Major) Early reports noted an increase in the excretion of tetracyclines during coadministration with sodium bicarbonate, and that the oral absorption of tetracyclines is reduced by sodium bicarbonate via increased gastric pH. However, conflicting data have been reported, and further study is needed. Two recent studies show no effect of oral sodium bicarbonate administration on tetracycline oral bioavailability. In one of these trials, coadministration with sodium bicarbonate was reported to have no effect on tetracycline urinary excretion, Cmax, or AUC. Until more information is available, avoid simultaneous administration of sodium bicarbonate and tetracyclines. When concurrent therapy is needed, stagger administration times by several hours to minimize the potential for interaction, and monitor for antimicrobial efficacy.
    Atovaquone: (Moderate) Concomitant use of tetracycline can reduce the plasma concentrations of atovaquone by approximately 40%. Parasitemia should be closely monitored in patients receiving atovaquone and tetracycline.
    Atovaquone; Proguanil: (Moderate) Concomitant use of tetracycline can reduce the plasma concentrations of atovaquone by approximately 40%. Parasitemia should be closely monitored in patients receiving atovaquone and tetracycline.
    Bexarotene: (Major) The concomitant use of systemic retinoid therapy, such as bexarotene, and systemic tetracyclines should be avoided due to the potential for increased cranial pressure and an increased risk of pseudotumor cerebri (benign intracranial hypertension). Pseudotumor cerebri has been reported with systemic retionoid use alone and early signs and symptoms include papilledema, headache, nausea, vomiting and visual disturbances.
    Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Separate administration of oral tetracyclines and bismuth subsalicylate by at least 2 to 3 hours. Coadministration may impair absorption of oral tetracyclines which may decrease their efficacy. Some data suggest that this interaction may only apply to administration with bismuth subsalicylate suspension.
    Bismuth Subsalicylate: (Moderate) Separate administration of oral tetracyclines and bismuth subsalicylate by at least 2 to 3 hours. Coadministration may impair absorption of oral tetracyclines which may decrease their efficacy. Some data suggest that this interaction may only apply to administration with bismuth subsalicylate suspension.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Separate administration of oral tetracyclines and bismuth subsalicylate by at least 2 to 3 hours. Coadministration may impair absorption of oral tetracyclines which may decrease their efficacy. Some data suggest that this interaction may only apply to administration with bismuth subsalicylate suspension.
    Calcium Acetate: (Major) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
    Calcium Carbonate: (Major) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
    Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Major) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
    Calcium Carbonate; Magnesium Hydroxide: (Major) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
    Calcium Carbonate; Risedronate: (Major) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
    Calcium Carbonate; Simethicone: (Major) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
    Calcium Chloride: (Major) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
    Calcium Gluconate: (Major) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
    Calcium: (Major) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
    Calcium; Vitamin D: (Major) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
    Carbenicillin: (Major) Avoid the coadministration of tetracycline antibiotics with penicillins as tetracyclines may interfere with the bactericidal action of penicillins.
    Carbetapentane; Guaifenesin; Phenylephrine: (Major) Concurrent administration of oral zinc salts with oral tetracyclines can decrease the absorption of these antiinfectives and possibly interfere with their therapeutic response. This is a result of the formation of insoluble chelates between zinc and the antiinfective. Oral zinc supplements should be administered at least 6 hours before or 2 hours after administering tetracyclines.
    Carbetapentane; Phenylephrine: (Major) Concurrent administration of oral zinc salts with oral tetracyclines can decrease the absorption of these antiinfectives and possibly interfere with their therapeutic response. This is a result of the formation of insoluble chelates between zinc and the antiinfective. Oral zinc supplements should be administered at least 6 hours before or 2 hours after administering tetracyclines.
    Chlorpheniramine; Pseudoephedrine: (Major) Concurrent administration of oral zinc salts with oral tetracyclines can decrease the absorption of these antiinfectives and possibly interfere with their therapeutic response. This is a result of the formation of insoluble chelates between zinc and the antiinfective. Oral zinc supplements should be administered at least 6 hours before or 2 hours after administering tetracyclines.
    Cholera Vaccine: (Major) Avoid the live cholera vaccine in patients that have received tetracycline within 14 days prior to vaccination. Concurrent administration of the live cholera vaccine with antibiotics active against cholera, such as tetracycline, may diminish vaccine efficacy and result in suboptimal immune response. A duration of fewer than 14 days between stopping antibiotics and vaccination might also be acceptable in some clinical settings if travel cannot be avoided before 14 days have elapsed after stopping antibiotics.
    Cholestyramine: (Major) Colestipol has been shown to reduce tetracycline absorption by roughly 50%. It is likely this is enough to cause a clinically significant effect. Although no data are available for other tetracyclines, or for cholestyramine, it should be assumed that any tetracycline antibiotic may be affected similarly by either cholestyramine or colestipol. Staggering oral doses of each agent is recommended to minimize this pharmacokinetic interaction. To minimize drug interactions, administer tetracyclines at least 1 hour before or at least 4 to 6 hours after the administration of cholestyramine. Since doxycycline undergoes enterohepatic recirculation, it may be even more susceptible to this drug interaction than the other tetracyclines.
    Chromium: (Major) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
    Colesevelam: (Moderate) Colesevelam may decrease the bioavailability of tetracyclines. To minimize potential for interactions, consider administering oral tetracyclines at least 4 hours before colesevelam. The manufacturer for colesevelam suggests monitoring serum drug concentrations and/or clinical effects for those drugs for which alterations in serum blood concentrations have a clinically significant effect on safety or efficacy.
    Colestipol: (Major) Colestipol has been shown to reduce tetracycline absorption by roughly 50%. It is likely this is enough to cause a clinically significant effect. Although no data are available for other tetracyclines, it should be assumed that any tetracycline antibiotic may be affected similarly by colestipol. Staggering oral doses of each agent is recommended to minimize this pharmacokinetic interaction; administer tetracyclines at least 1 hour before or at least 4 to 6 hours after the administration of colestipol. Since doxycycline undergoes enterohepatic recirculation, it may be even more susceptible to this drug interaction than the other tetracyclines.
    Dicloxacillin: (Major) Avoid the coadministration of tetracycline antibiotics with penicillins as tetracyclines may interfere with the bactericidal action of penicillins.
    Didanosine, ddI: (Major) Tetracyclines should not be administered simultaneously with didanosine, ddI chewable tablets or powder for oral solution. The buffering agents contained in didanosine tablets and powder reduce tetracycline absorption. Administer oral doses of tetracycline antibiotics 1 hour before or 4 hours after didanosine tablet or powder administration. The delayed-release didanosine capsules do not contain a buffering agent and would not be expected to interact with tetracycline antibiotics.
    Dienogest; Estradiol valerate: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available. (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Digoxin: (Major) Measure serum digoxin concentrations before initiating tetracyclines. Reduce digoxin concentrations by decreasing the digoxin dose by approximately 30 to 50% or by modifying the dosing frequency, and continue monitoring. In approximately 10% of patients, a small portion of a digoxin dose is metabolized in the gut by intestinal Eubacterium lentum, an anaerobic bacillus, to inactive digoxin reduction products (DRPs). DRPs have little cardiac activity due to poor cardiac receptor binding and rapid excretion. Certain antibiotics can reduce the activity of intestinal bacteria, which, in turn, may enhance digoxin bioavailability via decreased DRP formation and increased enterohepatic recycling of digoxin in some patients. The addition of tetracycline to digoxin therapy has been reported to increase the serum digoxin concentration by 100%. Digoxin toxicity has been reported in patients previously stabilized on digoxin who receive antibiotics that affect E. lentum, such as tetracyclines. Other antibiotics that have activity against E. lentum may produce similar effects on digoxin metabolism.
    Drospirenone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Drospirenone; Estetrol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Drospirenone; Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Drospirenone; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Elagolix; Estradiol; Norethindrone acetate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Estradiol Cypionate; Medroxyprogesterone: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Estradiol: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Estradiol; Levonorgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Estradiol; Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Estradiol; Norgestimate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Ethinyl Estradiol; Desogestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Ethinyl Estradiol; Ethynodiol Diacetate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Ethinyl Estradiol; Etonogestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Ethinyl Estradiol; Levonorgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Ethinyl Estradiol; Levonorgestrel; Ferrous bisglycinate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Ethinyl Estradiol; Norelgestromin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Ethinyl Estradiol; Norethindrone Acetate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Ethinyl Estradiol; Norethindrone Acetate; Ferrous fumarate: (Moderate) Iron salts or products that contain iron can decrease the oral bioavailability of tetracyclines. The ability of tetracyclines to chelate with divalent cations such as iron, however, varies depending on the particular antibiotic and when the antibiotic is administered with regard to the iron-containing product. Doxycycline chelates more avidly with iron than other tetracyclines. This pharmacokinetic interaction with iron can be minimized by staggering the doses of the antibiotic and iron by as much as possible. Administering iron-containing products 4 to 6 hours before or 1 hour after the oral tetracycline antibiotic dose will minimize the risk of antibiotic failure due to poor bioavailability. (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Ethinyl Estradiol; Norgestimate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Ethinyl Estradiol; Norgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Ferric Maltol: (Moderate) Iron salts or products that contain iron can decrease the oral bioavailability of tetracyclines. The ability of tetracyclines to chelate with divalent cations such as iron, however, varies depending on the particular antibiotic and when the antibiotic is administered with regard to the iron-containing product. Doxycycline chelates more avidly with iron than other tetracyclines. This pharmacokinetic interaction with iron can be minimized by staggering the doses of the antibiotic and iron by as much as possible. Administering iron-containing products 4 to 6 hours before or 1 hour after the oral tetracycline antibiotic dose will minimize the risk of antibiotic failure due to poor bioavailability.
    Food: (Major) Calcium salts that are present in foods and dairy products can form chelates with tetracycline and impair absorption. Administer tetracycline at least one hour prior to or two hours after a meal and/or milk. (Major) Iron salts that are present in foods and dairy products can form chelates with tetracycline and impair absorption. Administer tetracycline at least one hour prior to or two hours after a meal and/or milk.
    Halobetasol; Tazarotene: (Moderate) The manufacturer states that tazarotene should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as tetracyclines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Heparin: (Minor) Tetracyclines may partially counteract the anticoagulant actions of heparin, according to the product labels. However, this interaction is not likely of clinical significance in most patients since heparin therapy is adjusted to the partial thromboplastin time (aPTT) and other clinical parameters of the patient.
    Hetastarch; Dextrose; Electrolytes: (Major) Administration of oral magnesium-containing products with oral tetracycline antibiotics may form nonabsorbable complexes resulting in decreased absorption of tetracyclines. This can compromise therapeutic efficacy of the tetracycline agent. Do not administer oral magnesium-containing laxatives, antacids, dietary supplements, or other drugs within1 to 3 hours of taking an oral tetracycline. (Major) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
    Hydrochlorothiazide, HCTZ; Quinapril: (Major) Tetracycline absorption is reduced by about 28 to 37% with coadministration with quinapril, presumably due to the magnesium in the quinapril tablet.This interaction should be taken into account when prescribing tetracyclines with quinapril.
    Insoluble Prussian Blue: (Moderate) The binding of Insoluble Prussian Blue to some orally administered therapeutic drugs and essential nutrients is possible. The blood concentrations and/or clinical response to critical coadministered products should be monitored during Insoluble Prussian Blue therapy.
    Iron Salts: (Moderate) Iron salts or products that contain iron can decrease the oral bioavailability of tetracyclines. The ability of tetracyclines to chelate with divalent cations such as iron, however, varies depending on the particular antibiotic and when the antibiotic is administered with regard to the iron-containing product. Doxycycline chelates more avidly with iron than other tetracyclines. This pharmacokinetic interaction with iron can be minimized by staggering the doses of the antibiotic and iron by as much as possible. Administering iron-containing products 4 to 6 hours before or 1 hour after the oral tetracycline antibiotic dose will minimize the risk of antibiotic failure due to poor bioavailability.
    Iron Sucrose, Sucroferric Oxyhydroxide: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of tetracyclines will be significantly reduced by orally administered compounds that contain iron salts. To minimize the potential for this interaction, administer tetracycline antibiotics at least 1 hour before oral iron sucrose, sucroferric oxyhydroxide.
    Iron: (Moderate) Iron salts or products that contain iron can decrease the oral bioavailability of tetracyclines. The ability of tetracyclines to chelate with divalent cations such as iron, however, varies depending on the particular antibiotic and when the antibiotic is administered with regard to the iron-containing product. Doxycycline chelates more avidly with iron than other tetracyclines. This pharmacokinetic interaction with iron can be minimized by staggering the doses of the antibiotic and iron by as much as possible. Administering iron-containing products 4 to 6 hours before or 1 hour after the oral tetracycline antibiotic dose will minimize the risk of antibiotic failure due to poor bioavailability.
    Isotretinoin: (Major) Avoid the concomitant use of isotretinoin and systemic tetracyclines due to the potential for increased cranial pressure and an increased risk of pseudotumor cerebri (benign intracranial hypertension). Pseudotumor cerebri has been reported with both systemic retinoid and tetracycline use alone. Early signs and symptoms include papilledema, headache, nausea, vomiting, and visual disturbances.
    Lanthanum Carbonate: (Major) Oral compounds known to interact with antacids, like tetracyclines, should not be taken within 2 hours of dosing with lanthanum carbonate. If these agents are used concomitantly, space the dosing intervals appropriately. Monitor serum concentrations and clinical condition.
    Leuprolide; Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Levonorgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Lithium: (Major) The interaction between lithium and tetracycline appears variable. Both lithium toxicity and reduction in lithium concentrations have been reported during concurrent administration of tetracycline. Use of an alternative antibiotic should be considered in patients receiving lithium; however, if concurrent use of tetracycline is necessary, close monitoring of lithium levels and clinical response is recommended.
    Lomitapide: (Moderate) Caution should be exercised when lomitapide is used with other medications known to have potential for hepatotoxicity, such as tetracyclines. The effect of concomitant administration of lomitapide with other hepatotoxic medications is unknown. More frequent monitoring of liver-related tests may be warranted.
    Magnesium Citrate: (Major) Administration of oral magnesium citrate solution with oral tetracycline antibiotics may form nonabsorbable complexes resulting in decreased absorption of tetracyclines. Do not administer oral magnesium citrate solution within 1 to 3 hours of taking an oral tetracycline.
    Magnesium Hydroxide: (Moderate) Separate administration of tetracycline and antacids by 2 to 3 hours. Coadministration may impair absorption of tetracycline which may decrease its efficacy.
    Magnesium Salts: (Major) Administration of oral magnesium-containing products with oral tetracycline antibiotics may form nonabsorbable complexes resulting in decreased absorption of tetracyclines. This can compromise therapeutic efficacy of the tetracycline agent. Do not administer oral magnesium-containing laxatives, antacids, dietary supplements, or other drugs within1 to 3 hours of taking an oral tetracycline.
    Magnesium Sulfate; Potassium Sulfate; Sodium Sulfate: (Major) Administer tetracyclines at least 2 hours before or 6 hours after administration of magnesium sulfate; potassium sulfate; sodium sulfate. The absorption of tetracyclines may be reduced by chelation with magnesium sulfate.
    Magnesium: (Major) Administration of oral magnesium-containing products with oral tetracycline antibiotics may form nonabsorbable complexes resulting in decreased absorption of tetracyclines. This can compromise therapeutic efficacy of the tetracycline agent. Do not administer oral magnesium-containing laxatives, antacids, dietary supplements, or other drugs within1 to 3 hours of taking an oral tetracycline.
    Mestranol; Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Methotrexate: (Moderate) Oral antibiotics such as tetracyclines may decrease intestinal absorption of methotrexate or interfere with enterohepatic circulation by inhibiting bowel flora and suppressing metabolism of the drug by bacteria. Tetracyclines may displace methotrexate from protein binding sites leading to increased methotrexate levels. A case report describes a patient who received oral doxycycline in combination with her eleventh course of high-dose methotrexate. Methotrexate serum concentrations indicated a prolonged half-life and the patient developed severe gastrointestinal toxicity and myelosuppression including neutropenic fever. This resulted in two prolonged hospital stays and a delay in her next course of chemotherapy.
    Methoxsalen: (Moderate) Use methoxsalen and tetracyclines together with caution; the risk of severe burns/photosensitivity may be additive. If concurrent use is necessary, closely monitor patients for signs or symptoms of skin toxicity.
    Metoclopramide: (Minor) Metoclopramide can increase the rate or extent of absorption of tetracycline because of accelerated gastric emptying, which increases the contact time with the small bowel where this drug is absorbed.
    Mipomersen: (Moderate) Caution should be exercised when mipomersen is used with other medications known to have potential for hepatotoxicity, such as tetracyclines. The effect of concomitant administration of mipomersen with other hepatotoxic medications is unknown. More frequent monitoring of liver-related tests may be warranted.
    Molindone: (Major) The tablet formulation of molindone contains calcium sulfate as an excipient and the calcium ions may interfere with the absorption of tetracyclines. It may be advisable to consider an alternative to tetracycline treatment during molindone administration.
    Nafcillin: (Major) Avoid the coadministration of tetracycline antibiotics with penicillins as tetracyclines may interfere with the bactericidal action of penicillins.
    Neuromuscular blockers: (Moderate) Concomitant use of neuromuscular blockers and tetracyclines may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Norethindrone; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Iron salts or products that contain iron can decrease the oral bioavailability of tetracyclines. The ability of tetracyclines to chelate with divalent cations such as iron, however, varies depending on the particular antibiotic and when the antibiotic is administered with regard to the iron-containing product. Doxycycline chelates more avidly with iron than other tetracyclines. This pharmacokinetic interaction with iron can be minimized by staggering the doses of the antibiotic and iron by as much as possible. Administering iron-containing products 4 to 6 hours before or 1 hour after the oral tetracycline antibiotic dose will minimize the risk of antibiotic failure due to poor bioavailability. (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Norgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Omeprazole; Amoxicillin; Rifabutin: (Major) Avoid the coadministration of tetracycline antibiotics with penicillins as tetracyclines may interfere with the bactericidal action of penicillins.
    Omeprazole; Sodium Bicarbonate: (Major) Early reports noted an increase in the excretion of tetracyclines during coadministration with sodium bicarbonate, and that the oral absorption of tetracyclines is reduced by sodium bicarbonate via increased gastric pH. However, conflicting data have been reported, and further study is needed. Two recent studies show no effect of oral sodium bicarbonate administration on tetracycline oral bioavailability. In one of these trials, coadministration with sodium bicarbonate was reported to have no effect on tetracycline urinary excretion, Cmax, or AUC. Until more information is available, avoid simultaneous administration of sodium bicarbonate and tetracyclines. When concurrent therapy is needed, stagger administration times by several hours to minimize the potential for interaction, and monitor for antimicrobial efficacy.
    Oral Contraceptives: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Oxacillin: (Major) Avoid the coadministration of tetracycline antibiotics with penicillins as tetracyclines may interfere with the bactericidal action of penicillins.
    Penicillin G Benzathine: (Major) Avoid the coadministration of tetracycline antibiotics with penicillins as tetracyclines may interfere with the bactericidal action of penicillins.
    Penicillin G Benzathine; Penicillin G Procaine: (Major) Avoid the coadministration of tetracycline antibiotics with penicillins as tetracyclines may interfere with the bactericidal action of penicillins.
    Penicillin G Procaine: (Major) Avoid the coadministration of tetracycline antibiotics with penicillins as tetracyclines may interfere with the bactericidal action of penicillins.
    Penicillin G: (Major) Avoid the coadministration of tetracycline antibiotics with penicillins as tetracyclines may interfere with the bactericidal action of penicillins.
    Penicillin V: (Major) Avoid the coadministration of tetracycline antibiotics with penicillins as tetracyclines may interfere with the bactericidal action of penicillins.
    Penicillins: (Major) Avoid the coadministration of tetracycline antibiotics with penicillins as tetracyclines may interfere with the bactericidal action of penicillins.
    Photosensitizing agents (topical): (Moderate) Tetracyclines cause photosensitivity and may increase the photosensitizing effects photosensitizing agents used in photodynamic therapy. Prevention of photosensitivity includes adequate protection from sources of UV radiation and the use of protective clothing and sunscreens on exposed skin.
    Piperacillin: (Major) Avoid the coadministration of tetracycline antibiotics with penicillins as tetracyclines may interfere with the bactericidal action of penicillins.
    Piperacillin; Tazobactam: (Major) Avoid the coadministration of tetracycline antibiotics with penicillins as tetracyclines may interfere with the bactericidal action of penicillins.
    Polycarbophil: (Major) Coadministration of calcium polycarbophil with orally administered tetracyclines can decrease the absorption of tetracyclines; oral doses of tetracyclines should be given 2 hours before or after the administration of calcium polycarbophil. Each 625 mg of calcium polycarbophil contains a substantial amount of calcium (approximately 125 mg). This effect is presumably due to the chelation of the antibiotic by the calcium.
    Polyethylene Glycol; Electrolytes: (Major) Administer tetracyclines at least 2 hours before or 6 hours after administration of magnesium sulfate; potassium sulfate; sodium sulfate. The absorption of tetracyclines may be reduced by chelation with magnesium sulfate.
    Polyethylene Glycol; Electrolytes; Ascorbic Acid: (Major) Administer tetracyclines at least 2 hours before or 6 hours after administration of magnesium sulfate; potassium sulfate; sodium sulfate. The absorption of tetracyclines may be reduced by chelation with magnesium sulfate.
    Polysaccharide-Iron Complex: (Moderate) Iron salts or products that contain iron can decrease the oral bioavailability of tetracyclines. The ability of tetracyclines to chelate with divalent cations such as iron, however, varies depending on the particular antibiotic and when the antibiotic is administered with regard to the iron-containing product. Doxycycline chelates more avidly with iron than other tetracyclines. This pharmacokinetic interaction with iron can be minimized by staggering the doses of the antibiotic and iron by as much as possible. Administering iron-containing products 4 to 6 hours before or 1 hour after the oral tetracycline antibiotic dose will minimize the risk of antibiotic failure due to poor bioavailability.
    Porfimer: (Major) Avoid coadministration of porfimer with tetracyclines due to the risk of increased photosensitivity. Porfimer is a light-activated drug used in photodynamic therapy; all patients treated with porfimer will be photosensitive. Concomitant use of other photosensitizing agents like tetracyclines may increase the risk of a photosensitivity reaction.
    Pyridostigmine: (Moderate) Parenteral administration of high doses of certain antibiotics such as tetracyclines may intensify or produce neuromuscular block through their own pharmacologic actions. If unexpected prolongation of neuromuscular block or resistance to its reversal with pyridostigmine occurs, consider the possibility of an antibiotic effect.
    Pyridoxine, Vitamin B6: (Major) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
    Quinapril: (Major) Tetracycline absorption is reduced by about 28 to 37% with coadministration with quinapril, presumably due to the magnesium in the quinapril tablet.This interaction should be taken into account when prescribing tetracyclines with quinapril.
    Quinine: (Moderate) Concomitant administration of quinine and tetracycline may result in higher quinine plasma concentrations. It is recommended that patients be monitored closely for quinine-associated adverse reactions if tetracycline is given with quinine.
    Relugolix; Estradiol; Norethindrone acetate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Segesterone Acetate; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Sodium Bicarbonate: (Major) Early reports noted an increase in the excretion of tetracyclines during coadministration with sodium bicarbonate, and that the oral absorption of tetracyclines is reduced by sodium bicarbonate via increased gastric pH. However, conflicting data have been reported, and further study is needed. Two recent studies show no effect of oral sodium bicarbonate administration on tetracycline oral bioavailability. In one of these trials, coadministration with sodium bicarbonate was reported to have no effect on tetracycline urinary excretion, Cmax, or AUC. Until more information is available, avoid simultaneous administration of sodium bicarbonate and tetracyclines. When concurrent therapy is needed, stagger administration times by several hours to minimize the potential for interaction, and monitor for antimicrobial efficacy.
    Sodium Ferric Gluconate Complex; ferric pyrophosphate citrate: (Moderate) Iron salts or products that contain iron can decrease the oral bioavailability of tetracyclines. The ability of tetracyclines to chelate with divalent cations such as iron, however, varies depending on the particular antibiotic and when the antibiotic is administered with regard to the iron-containing product. Doxycycline chelates more avidly with iron than other tetracyclines. This pharmacokinetic interaction with iron can be minimized by staggering the doses of the antibiotic and iron by as much as possible. Administering iron-containing products 4 to 6 hours before or 1 hour after the oral tetracycline antibiotic dose will minimize the risk of antibiotic failure due to poor bioavailability.
    Sodium picosulfate; Magnesium oxide; Anhydrous citric acid: (Major) Prior or concomitant use of antibiotics with sodium picosulfate; magnesium oxide; anhydrous citric acid may reduce efficacy of the bowel preparation as conversion of sodium picosulfate to its active metabolite bis-(p-hydroxy-phenyl)-pyridyl-2-methane (BHPM) is mediated by colonic bacteria. If possible, avoid coadministration. Certain antibiotics (i.e., tetracyclines and quinolones) may chelate with the magnesium in sodium picosulfate; magnesium oxide; anhydrous citric acid solution. Therefore, these antibiotics should be taken at least 2 hours before and not less than 6 hours after the administration of sodium picosulfate; magnesium oxide; anhydrous citric acid solution.
    Sodium Sulfate; Magnesium Sulfate; Potassium Chloride: (Major) Administration of oral magnesium-containing products with oral tetracycline antibiotics may form nonabsorbable complexes resulting in decreased absorption of tetracyclines. This can compromise therapeutic efficacy of the tetracycline agent. Do not administer oral magnesium-containing laxatives, antacids, dietary supplements, or other drugs within1 to 3 hours of taking an oral tetracycline.
    St. John's Wort, Hypericum perforatum: (Moderate) St. John's Wort is known to cause photosensitivity. In theory it is possible that additive photosensitizing effects may result from the concomitant use of St. John's Wort with other photosensitizing drugs such as tetracyclines.
    Sucralfate: (Moderate) Sucralfate should be given 2 hours before or after the oral administration of tetracyclines. Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain aluminum salts, calcium salts, iron salts, magnesium salts, and/or zinc salts. Sucralfate, because it contains aluminum in its structure and due to its mechanism of action, can bind with tetracyclines in the GI tract, reducing the bioavailability of these agents.
    Sulfonylureas: (Moderate) Additive photosensitization may be seen with concurrent administration of sulfonylureas and other photosensitizing agents including tetracyclines. Prevention of photosensitivity includes adequate protection from sources of UV radiation (e.g., avoiding sun exposure and tanning booths) and the use of protective clothing and sunscreens on exposed skin.
    Tazarotene: (Moderate) The manufacturer states that tazarotene should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as tetracyclines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Ticarcillin: (Major) Avoid the coadministration of tetracycline antibiotics with penicillins as tetracyclines may interfere with the bactericidal action of penicillins.
    Ticarcillin; Clavulanic Acid: (Major) Avoid the coadministration of tetracycline antibiotics with penicillins as tetracyclines may interfere with the bactericidal action of penicillins.
    Tretinoin, ATRA: (Major) The concomitant use of systemic tretinoin, ATRA and systemic tetracyclines should be avoided due to the potential for increased intracranial pressure and an increased risk of pseudotumor cerebri (benign intracranial hypertension). Pseudotumor cerebri has been reported with systemic retinoid use alone and early signs and symptoms include papilledema, headache, nausea, vomiting and visual disturbances. In addition, a manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as tetracyclines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Verteporfin: (Moderate) Use caution if coadministration of verteporfin with tetracyclines is necessary due to the risk of increased photosensitivity. Verteporfin is a light-activated drug used in photodynamic therapy; all patients treated with verteporfin will be photosensitive. Concomitant use of other photosensitizing agents like tetracyclines may increase the risk of a photosensitivity reaction.
    Warfarin: (Moderate) Tetracyclines may increase the action of warfarin and other oral anticoagulants by either impairing prothrombin utilization or, possibly, decreasing production of vitamin K because of its antiinfective action on gut bacteria. Monitor patients for signs and symptoms of bleeding. Additionally, increased monitoring of the INR, especially during initiation and upon discontinuation of the antibiotic, may be necessary
    Zinc Salts: (Major) Concurrent administration of oral zinc salts with oral tetracyclines can decrease the absorption of these antiinfectives and possibly interfere with their therapeutic response. This is a result of the formation of insoluble chelates between zinc and the antiinfective. Oral zinc supplements should be administered at least 6 hours before or 2 hours after administering tetracyclines.
    Zinc: (Major) Concurrent administration of oral zinc salts with oral tetracyclines can decrease the absorption of these antiinfectives and possibly interfere with their therapeutic response. This is a result of the formation of insoluble chelates between zinc and the antiinfective. Oral zinc supplements should be administered at least 6 hours before or 2 hours after administering tetracyclines.

    PREGNANCY AND LACTATION

    Pregnancy

    Tetracycline is classified as FDA pregnancy category D. All tetracyclines have a detrimental effect on the skeletal development and bone growth of the fetus or child. Do not use tetracycline in the second half of pregnancy unless benefits from treatment outweigh the risks to the fetus; use with extreme caution. In a nested, case-control study (n = 87,020 controls; 8,702 cases) within the Quebec Pregnancy Cohort, tetracycline use during early pregnancy was associated with an increased risk of spontaneous abortion (adjusted odds ratio (aOR) 2.59, 95% CI: 1.97 to 3.41, 67 exposed cases); residual confounding by severity of infection may be a potential limitation of this study. Guidelines suggest tetracycline may be used for the treatment of uncomplicated malaria during pregnancy in rare instances if other options are not available or are not tolerated and benefit of use outweighs risks.

    Tetracyclines are distributed in small amounts into breast milk. In general, manufacturers recommend that tetracycline antibiotics not be used in breast feeding mothers due to a theoretical risk of causing teeth discoloration, enamel hypoplasia, inhibition of linear skeletal growth, oral and vaginal thrush, or photosensitivity reactions in the nursing infant. However, because tetracyclines bind to calcium in the maternal breast milk, the risk for oral absorption by the infant is minimal. The American Academy of Pediatrics considers tetracycline to be compatible with breast-feeding. Data are available regarding milk concentrations and infant serum concentrations following tetracycline use in breast-feeding women. In a study using a microbiologic assay, milk tetracycline concentrations were measured in an unspecified number of nursing mothers at 9 am after various dosages of tetracycline during the previous days. Whether the women had mastitis and the time postpartum were not stated. Milk levels were reported as 2.5 mg/L after a daily dose of 1 gram orally for 3 days, to 2 mg/L after a daily dose of 1.5 grams orally for 2 days, and to 2.5 mg/L after a daily dose of 2 grams orally for 3 days. In these women, no adverse effects were noted in an unspecified number of their breast-fed infants; the ages of the infants and extent of breast-feeding were also not stated. In another study, 5 women were given oral tetracycline (500 mg 4 times a day for 3 days); milk levels ranged from 0.43 to 2.58 mg/L (times not specified). Their infants were allowed to nurse and the infants' tetracycline concentrations were undetectable (< 50 mcg/L) in serum and no adverse effects were observed. Finally, in an observational study of 251 women, 23.8% of nursing mothers received tetracycline during breast-feeding; no gross adverse effect occurred in any of the breast-fed infants. Studies of long-term tetracycline use in breast-feeding are lacking. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    Tetracycline is generally bacteriostatic against most organisms, but high concentrations of tetracyclines can be bactericidal. Bacteriostatic action appears to be a result of reversible binding to ribosomal units of susceptible organisms and inhibition of protein synthesis. Tetracyclines gain access to the ribosome after passive diffusion through porin channels in the bacterial membrane. An active transport process also exists in bacterial cells. Tetracyclines bind to the 30 S ribosomal subunit, which prevents binding of tRNA to the mRNA-ribosome complex, thus interfering with protein synthesis. Only multiplying organisms are affected. In general, gram-positive bacteria are more susceptible than are gram-negative bacteria. Tetracycline resistance in community-acquired MRSA (CA-MRSA) isolates is primarily associated with the tetK gene.The tetM resistance gene confers resistance to the entire class; however, the tetK gene confers resistance to tetracycline and an inducible resistance to doxycyline, but has no impact on minocycline susceptibility.
     
    The action of tetracycline in the treatment of acne vulgaris has not been fully established but is believed to be due in part to its antibacterial actions. Skin bacteria produce lipase that breaks down triglycerides present in sebum into free fatty acids, which are comedogenic and may be the cause of the inflammatory lesions of acne. Reduction in the number of lipase-producing bacteria or inhibition of lipase production are two possible mechanisms of tetracyclines. Several other mechanisms have been proposed but not studied.

    PHARMACOKINETICS

    Tetracycline is administered orally. It is no longer available for parenteral administration.
     
    Tetracycline is widely distributed into body fluids, including CSF. All tetracyclines tend to concentrate in bone, liver, tumors, spleen, and teeth. They cross the placenta and are distributed into breast milk. Tetracycline is about 65% bound to plasma protein and does not appear to undergo hepatic metabolism. It does undergo enterohepatic circulation and is excreted in the feces by way of the bile. Some fecal excretion is due to incomplete gastrointestinal absorption and occurs even from parenteral administration because of enterohepatic circulation. The primary excretion route is renal (about 60%). The serum half-life of tetracycline hydrochloride is between 6 and 12 hours in adults with normal renal function but is greatly increased in patients with severely impaired renal function.

    Oral Route

    Tetracycline oral absorption is about 75—77% in the fasting state. Absorption takes place mainly in the stomach and upper intestine. As the dosage is increased, the percentage absorbed decreases. Divalent and trivalent cations that are present in antacids and dairy products reduce absorption through chelation (see Drug Interactions).

    Other Route(s)

    Periodontal Route
    Tetracycline periodontal fibers are inserted into periodontal pockets. The fiber releases tetracycline in vitro at a rate of approximately 2 mcg/cm/hour. Tetracycline is released at this continuous rate for 10 days at concentrations far exceeding inhibitory concentrations for most periodontal organisms. Serum concentrations remain below the lower limit of assay detection (< 0.1 mcg/ml) during treatment of 11 teeth (average tetracycline dose of 105 mg).