Tetracycline is semisynthetically produced from chlortetracycline. Tetracycline is available in oral and topical preparations, including an ophthalmic ointment.It is classified as a short-acting tetracycline, although this classification scheme is somewhat artificial since tetracycline can be dosed at longer intervals than usually occurs in clinical practice. It has a wide spectrum of activity against many gram-negative and gram-positive organisms, but is inactive against viruses and fungi. Tetracycline can be used for acne vulgaris, malaria, and rickettsial infections, although other antibacterials may be preferred. It is generally not recommended for routine use in pediatric patients younger than 8 years due to the potential for staining of permanent teeth.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific 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.
Extemporaneous Compounding-Oral
NOTE: Extemporaneously compounded oral tetracycline suspension is not FDA-approved.
Extemporaneous preparation of 25 mg/mL tetracycline oral suspension
-Empty the powder from six 500-mg tetracycline capsules in a glass mortar.
-Add 20 mL of vehicle (1:1 mixture of Ora-Plus and Ora-Sweet/Ora-Sweet NF or Cherry Syrup [cherry syrup concentrate diluted 1:4 with simple syrup]) and mix to a uniform paste.
-Add the vehicle in geometric portions and mix thoroughly after each addition.
-Transfer the mixture into an amber plastic bottle.
-Add enough vehicle to bring the final volume to 120 mL.
-Label the bottle with 'Shake well before use' and 'Protect from light'.
-Storage:
--Prepared with Ora-Sweet and Ora-Plus: The oral suspension is stable for 28 days when stored at room temperature (25 degrees C) or refrigerated (5 degrees C).
-Prepared with Ora-Sweet SF and Ora-Plus: The oral suspension is stable for 7 days when stored at room temperature (25 degrees C) or 10 days when stored refrigerated (5 degrees C).
-Prepared with Cherry Syrup: The oral suspension is stable for 7 days when stored at room temperature (25 degrees C) or refrigerated (5 degrees C).
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.
When given over prolonged periods, tetracyclines can produce brown-black microscopic discoloration of the thyroid glands, but no abnormalities of thyroid function have been reported.
Benign increased intracranial pressure (pseudotumor cerebri) can occur during therapy with tetracycline and is usually reversible following discontinuation of the drug but may produce permanent sequelae. The usual clinical manifestations of pseudotumor cerebri are headache, diplopia, vision loss, blurred vision, and papilledema found on fundoscopy. Women of childbearing age who are overweight or have a history of intracranial hypertension are at greater risk. Bulging fontanels in infants have also been reported.
Diarrhea, nausea, vomiting, epigastric distress, glossitis, black hairy tongue (tongue discoloration), dysphagia, enterocolitis, inflammatory lesions, and anorexia are all possible GI side effects of tetracycline. These effects can be alleviated by taking the drug with large amounts of fluid and avoiding dosage at bedtime. Hepatotoxicity and hepatic failure have been reported in patients receiving large doses during renal impairment. Abdominal complaints may suggest hepatotoxicity, although the incidence has been reported to be about 4.7%. Rare cases of esophagitis and esophageal ulceration have been reported in patients receiving tetracycline capsules. Tetracycline-induced esophagitis is characterized by sudden onset odynophagia, retrosternal pain, and dysphagia. Risk factors include taking the medication without water and at night. Symptoms usually resolve within days to weeks after stopping the medication.
Microbial overgrowth and superinfection can occur with antibiotic use. C. difficile-associated diarrhea (CDAD) or pseudomembranous colitis has been reported with tetracycline. If pseudomembranous colitis is suspected or confirmed, ongoing antibacterial therapy not directed against C. difficile may need to be discontinued. Institute appropriate fluid and electrolyte management, protein supplementation, C. difficile-directed antibacterial therapy, and surgical evaluation as clinically appropriate. Anogenital candidiasis has also been reported.
Photosensitivity, if apparent, can appear within minutes of taking the tetracycline if the patient is exposed to direct sunlight or UV light. Warning signs, including tingling and burning of the hands, feet, and nose, may indicate latent photosensitivity. If the drug is discontinued, symptoms are usually alleviated within 1-2 days. Sunscreens seem to provide only limited protection, and a severe response may necessitate treatment with corticosteroids or antihistamines. Maculopapular rash and erythematous rash (erythema) have occurred. Nail discoloration/oncholysis has been rarely reported. Exfoliative dermatitis is uncommon. Other reported hypersensitivity reactions include urticaria, angioedema, anaphylactoid reactions, anaphylactoid purpura, pericarditis, exacerbation of lupus erythematosus (lupus-like symptoms), and serum sickness like reactions, such as fever, rash (unspecified), and arthralgia..
Tooth discoloration has been seen in children who received a tetracycline antibiotic, but this reaction has also been reported in adults. Enamel hypoplasia can result. Although this is not typically thought of as teratogenesis, some references include tetracyclines in lists of teratogenic drugs. While isolated cases of major fetal malformations have been reported in offspring of mothers who received a tetracycline drug during pregnancy, analysis of the data does not support an association between these drugs and these major malformations (e.g., oral clefts, spina bifida, polydactyly). Limited data exist which support a possible risk of minor malformations (e.g., hypospadias, inguinal hernia).
Tetracycline-induced hemolytic anemia, thrombocytopenia, thrombotic thrombocytopenic purpura (TTP), neutropenia, eosinophilia may occur. Patients should be evaluated regularly in these instances.
Adverse renal effects of tetracyclines are usually a problem only for patients with seriously impaired renal function. The antianabolic action of the tetracyclines may cause an increase in BUN (azotemia). Lower doses may be necessary, and renal function should be monitored before and during treatment in patients with serious renal impairment. Historically, a Fanconi syndrome has been associated with use of outdated or degraded tetracycline products , so shelf-life dates for tetracycline products should be strictly adhered to. The cases of the Fanconi-like syndrome resulted in modifications in formulations of tetracycline class products on the market today, so this complication is unlikely to recur.
The Jarisch-Herxheimer reaction is a self-limiting systemic reaction that has been reported in the setting of spirochete infections, such as Lyme disease, syphilis, relapsing fever, and leptospirosis, after the initiation of antimicrobial therapy. It is characterized by fever, chills, myalgias, headache, exacerbation of cutaneous lesions, tachycardia, hyperventilation, vasodilation with flushing, and mild hypotension. Less commonly, symptoms may include meningitis, pulmonary failure, hepatic and renal dysfunction, myocardial injury, premature uterine contractions in pregnant patients, and worsening cerebral function as well as strokes and seizures. The reaction has been noted in up to 30% of patients with early Lyme disease. The timing of the reaction varies by underlying infection but typically presents within a few hours after the initiation of antibiotics. For Lyme disease, the reaction usually begins within 1 to 2 hours after starting therapy and disappears within 12 to 24 hours. The reaction after treatment in syphilis usually starts at 4 hours, peaks at 8 hours, and subsides by 16 hours whereas it starts at about 1 to 2 hours, peaks at 4 hours, and subsides by 8 hours after treatment in relapsing fever. The pathogenesis of this reaction is unknown but may be due to the release of spirochetal heat-stable pyrogen. Fluids and antipyretics can be used to alleviate symptoms and duration of the reaction if severe.
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.
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 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.
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.
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.
Dose adjustment may be required in patients with hepatic disease because hepatic excretion of tetracycline into bile can be delayed in these patients.
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.
In patients undergoing surgery with methoxyflurane anesthesia, concurrent use of tetracycline can increase the risk of nephrotoxicity (sometimes fatal).
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.
Consider pseudomembranous colitis in patients presenting with diarrhea after antibacterial use. Careful medical history is necessary as pseudomembranous colitis has been reported to occur over 2 months after the administration of antibacterial agents. Almost all antibacterial agents, including tetracycline, have been associated with pseudomembranous colitis or C. difficile-associated diarrhea (CDAD) which may range in severity from mild to life-threatening. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.
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.
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.
Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: Acinetobacter sp., Actinomyces sp., Bacillus anthracis, Bacteroides sp., Balantidium coli, Bartonella bacilliformis, Borrelia recurrentis, Brucella sp., Campylobacter fetus, Chlamydia trachomatis, Chlamydophila psittaci, Clostridium sp., Cutibacterium acnes, Entamoeba histolytica, Entamoeba sp., Escherichia coli, Francisella tularensis, Fusobacterium fusiforme, Haemophilus ducreyi, Haemophilus influenzae (beta-lactamase negative), Haemophilus influenzae (beta-lactamase positive), Klebsiella aerogenes, Klebsiella granulomatis, Klebsiella sp., Listeria monocytogenes, Mycoplasma pneumoniae, Neisseria gonorrhoeae, Rickettsia sp., Shigella sp., Staphylococcus aureus (MRSA), Staphylococcus aureus (MSSA), Streptococcus pneumoniae, Streptococcus pyogenes (group A beta-hemolytic streptococci), Treponema pallidum, Treponema pertenue, Vibrio cholerae, Yersinia pestis
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.
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:
Oral dosage:
Adults: 500 mg PO every 6 hours for 6 to 12 months after IV therapy. Shorter courses may be appropriate for less extensive infections.
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 the treatment of primary, secondary, or early latent syphilis 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 the treatment of 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 is the FDA-approved dosage.
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) is the FDA-approved dosage.
For the treatment of chlamydia infection due to C. trachomatis, including urethritis, cervicitis, proctitis, chlamydial conjunctivitis, trachoma, and lymphogranuloma venereum:
Oral dosage:
Adults: Not recommended by guidelines. The FDA-approved dosage is 500 mg PO 4 times daily for at least 7 days.
Children and Adolescents 9 to 17 years: Not recommended by guidelines. The FDA-approved dosage is 25 to 50 mg/kg/day PO in 4 divided doses (Max: 500 mg/dose).
For the treatment of granuloma inguinale (Donovanosis):
Oral dosage:
Adults: Not recommended by 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: Not recommended by 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: Not recommended by 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: Not recommended by 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 every 6 hours for at least 10 to 14 days after fever resolves.
Children and Adolescents 9 to 17 years: 25 to 50 mg/kg/day PO in 4 divided doses (Max: 500 mg/dose) for at least 10 to 14 days after fever resolves.
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 of anthrax:
-for the treatment of cutaneous anthrax without aerosol exposure or signs and symptoms of meningitis:
Oral dosage:
Adults: 500 mg PO every 6 hours for 7 to 10 days or until clinical criteria for stability are met.
Children and Adolescents 9 to 17 years: 12.5 mg/kg/dose (Max: 500 mg/dose) PO every 6 hours for 7 to 10 days or until clinical criteria for stability are met.
Infants and Children 1 month to 8 years*: 12.5 mg/kg/dose (Max: 500 mg/dose) PO every 6 hours for 7 to 10 days or until clinical criteria for stability are met.
-for the treatment of cutaneous anthrax with aerosol exposure and without signs and symptoms of meningitis:
Oral dosage:
Adults: 500 mg PO every 6 hours for 7 to 10 days or until clinical criteria for stability are met and then transition to a postexposure prophylaxis regimen to complete a 42- to 60-day total treatment course depending on vaccine status and immunocompetence.
Children and Adolescents 9 to 17 years: 12.5 mg/kg/dose (Max: 500 mg/dose) PO every 6 hours for 7 to 10 days or until clinical criteria for stability are met and then transition to a postexposure prophylaxis regimen to complete a 60-day total treatment course.
Infants and Children 1 month to 8 years*: 12.5 mg/kg/dose (Max: 500 mg/dose) PO every 6 hours for 7 to 10 days or until clinical criteria for stability are met and then transition to a postexposure prophylaxis regimen to complete a 60-day total treatment course.
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 infectious diarrhea and gastroenteritis, including amebiasis, campylobacteriosis, cholera, and shigellosis:
-for the treatment of intestinal amebiasis as adjunctive therapy:
Oral dosage:
Adults: 500 mg PO twice daily or 250 mg PO every 6 hours for mild to moderate infections or 500 mg PO every 6 hours for severe infections.
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 campylobacteriosis:
Oral dosage:
Adults: 500 mg PO twice daily or 250 mg PO every 6 hours for mild to moderate infections or 500 mg PO every 6 hours for severe infections.
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 cholera:
Oral dosage:
Adults: 500 mg PO every 6 hours for 3 days. The FDA-approved dose is 500 mg PO twice daily or 250 mg PO every 6 hours for mild to moderate infections or 500 mg PO every 6 hours for severe infections.
Children and Adolescents 9 to 17 years: 12.5 mg/kg/dose (Max: 500 mg/dose) PO every 6 hours for 3 days. The FDA-approved dose is 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. The FDA-approved dose is 500 mg PO twice daily or 250 mg PO every 6 hours for mild to moderate infections or 500 mg PO every 6 hours for severe infections.
Children and Adolescents 9 to 17 years: Guidelines recommend against the use of tetracycline. The FDA-approved dose is 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 acne rosacea*:
Oral dosage:
Adults: 250 to 500 mg PO twice daily.
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 bubonic or pharyngeal plague infection:
Oral dosage:
Adults: 500 mg PO every 6 hours for 10 to 14 days as an alternative therapy in nonpregnant patients. Monotherapy is recommended for stable patients with naturally occurring plague, although dual therapy can be considered for patients with large buboes. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment in patients infected after intentional release of Y. pestis.
Children and Adolescents 9 to 17 years: 10 mg/kg/dose (Max: 500 mg/dose) PO every 6 hours for 10 to 14 days as an alternative therapy. Monotherapy is recommended for stable patients with naturally occurring plague, although dual therapy can be considered for patients with large buboes. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment in patients infected after intentional release of Y. pestis.
Infants* and Children 1 to 8 years*: 10 mg/kg/dose PO every 6 hours for 10 to 14 days as an alternative therapy. Monotherapy is recommended for stable patients with naturally occurring plague, although dual therapy can be considered for patients with large buboes. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment in patients infected after intentional release of Y. pestis.
For plague prophylaxis*:
-for pre-exposure prophylaxis*:
Oral dosage:
Adults: 500 mg PO every 6 hours until 48 hours after the last perceived exposure as an alternative therapy.
Infants, Children, and Adolescents: 10 mg/kg/dose (Max: 500 mg/dose) PO every 6 hours until 48 hours after the last perceived exposure as an alternative therapy.
-for postexposure prophylaxis*:
Oral dosage:
Adults: 500 mg PO every 6 hours for 7 days as an alternative therapy.
Infants, Children, and Adolescents: 10 mg/kg/dose (Max: 500 mg/dose) PO every 6 hours for 7 days as an alternative therapy.
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*:
-for Helicobacter pylori (H. pylori) eradication* as part of initial bismuth-based quadruple therapy:
Oral dosage:
Adults: 500 mg PO 4 times daily in combination with bismuth subsalicylate, metronidazole, and a proton pump inhibitor (PPI) for 10 to 14 days.
Children and Adolescents 9 to 17 years: 25 to 50 mg/kg/day (Max: 2 g/day) PO in 4 divided doses in combination with bismuth subsalicylate, metronidazole, and a proton pump inhibitor (PPI) for 14 days.
-for Helicobacter pylori (H. pylori) eradication* as part of salvage bismuth-based quadruple therapy:
Oral dosage:
Adults: 500 mg PO 4 times daily in combination with bismuth subsalicylate, metronidazole, and a proton pump inhibitor (PPI) for 14 days.
Children and Adolescents 9 to 17 years: 25 to 50 mg/kg/day (Max: 2 g/day) PO in 4 divided doses in combination with bismuth subsalicylate, metronidazole, and a proton pump inhibitor (PPI) for 14 days.
-for Helicobacter pylori (H. pylori) eradication* as part of an alternative bismuth-based quadruple therapy:
Oral dosage:
Adults: 500 mg PO 4 times daily in combination with bismuth subsalicylate, a proton pump inhibitor (PPI), and amoxicillin, clarithromycin, levofloxacin, or metronidazole for 14 days.
For the treatment of uncomplicated malaria* due to P. falciparum, P. vivax, P. ovale, P. malariae, or P. knowlesi:
Oral dosage:
Adults: 250 mg PO 4 times daily for 7 days plus quinine. For P. vivax or P. ovale infections, add primaquine phosphate. Guidelines recommend for chloroquine-resistant infections and for infections of unknown resistance in combination with quinine; may also use for chloroquine-sensitive infections if necessary.
Children and Adolescents 8 to 17 years: 25 mg/kg/day PO divided 4 times daily (Max: 250 mg/dose) for 7 days plus quinine. For P. vivax or P. ovale infections, add primaquine phosphate. Guidelines recommend for chloroquine-resistant infections and for infections of unknown resistance in combination with quinine; may also use for chloroquine-sensitive infections if necessary.
Children younger 1 to 7 years: 25 mg/kg/day PO divided 4 times daily (Max: 250 mg/dose) for 7 days plus quinine. For P. vivax or P. ovale infections, add primaquine phosphate. Guidelines recommend for chloroquine-resistant infections and for infections of unknown resistance in combination with quinine; may also use for chloroquine-sensitive infections if necessary. 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.
For the treatment of small intestinal bacterial overgrowth*:
Oral dosage:
Adults: 250 mg PO every 6 hours for 7 to 10 days.
Children and Adolescents 9 to 17 years: 25 to 50 mg/kg/day PO in 4 divided doses (Max: 250 mg/dose) for 7 to 10 days.
For the treatment of rat-bite fever*:
Oral dosage:
Adults: 500 mg PO every 6 hours for 14 days as an alternative.
Infants, Children, and Adolescents: 25 to 50 mg/kg/day (Max: 2 g/day) PO divided every 6 hours for 14 days as an alternative.
For postexposure anthrax prophylaxis*:
-for postexposure anthrax prophylaxis* after nonaerosol exposure (cutaneous or ingestion):
Oral dosage:
Adults: 500 mg PO every 6 hours for 7 days after exposure.
Infants, Children, and Adolescents: 12.5 mg/kg/dose (Max: 500 mg/dose) PO every 6 hours for 7 days after exposure.
-for postexposure anthrax prophylaxis* after aerosol exposure:
Oral dosage:
Adults 66 years and older: 500 mg PO every 6 hours for 60 days after exposure.
Adults 18 to 65 years: 500 mg PO every 6 hours for 60 days after exposure. For immunocompetent, nonpregnant persons who received the anthrax vaccine, may decrease duration to 42 days after first antibiotic dose or 2 weeks after the last vaccine dose, whichever occurs later.
Infants, Children, and Adolescents: 12.5 mg/kg/dose (Max: 500 mg/dose) PO every 6 hours for 60 days after exposure.
Maximum Dosage Limits:
-Adults
2 g/day PO.
-Geriatric
2 g/day PO.
-Adolescents
50 mg/kg/day PO (Max: 2 g/day).
-Children
9 to 12 years: 50 mg/kg/day (Max: 2 g/day) PO.
1 to 8 years: Safety and efficacy have not been established; however, doses up to 40 mg/kg/day (Max: 2 g/day) PO have been used off-label.
-Infants
Safety and efficacy have not been established; however, doses up to 40 mg/kg/day PO have been used off-label.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Dose adjustment of tetracycline may be required in patients with hepatic impairment due to potential for reduced excretion and a prolonged half-life.
Patients with Renal Impairment Dosing
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.
*non-FDA-approved indication
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.
Aminolevulinic Acid: (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.
Amoxicillin: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
Amoxicillin; Clarithromycin; Omeprazole: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
Amoxicillin; Clavulanic Acid: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
Ampicillin: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
Ampicillin; Sulbactam: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
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.
Atracurium: (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.
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: (Moderate) 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: (Moderate) 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: (Moderate) 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: (Moderate) 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; Simethicone: (Moderate) 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: (Moderate) 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: (Moderate) 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: (Moderate) 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: (Moderate) 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: (Moderate) 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.
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: (Moderate) 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.
Cisatracurium: (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.
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.
Desogestrel; 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.
Dicloxacillin: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
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: (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; 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; 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.
Ethynodiol Diacetate; 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.
Etonogestrel; 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.
Ferric Maltol: (Moderate) Separate administration of tetracyclines and iron by 2 to 3 hours. Iron may decrease the oral bioavailability of tetracyclines.
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.
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) Separate administration of tetracyclines and iron by 2 to 3 hours. Iron may decrease the oral bioavailability of tetracyclines.
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) Separate administration of tetracyclines and iron by 2 to 3 hours. Iron may decrease the oral bioavailability of tetracyclines.
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.
Lansoprazole; Amoxicillin; Clarithromycin: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
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.
Levonorgestrel; 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.
Levonorgestrel; Ethinyl Estradiol; 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. (Moderate) Separate administration of tetracyclines and iron by 2 to 3 hours. Iron may decrease the oral bioavailability of tetracyclines.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (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. (Moderate) Separate administration of tetracyclines and iron by 2 to 3 hours. Iron may decrease the oral bioavailability of tetracyclines.
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: (Moderate) Administer magnesium citrate at least 3 hours before or 3 hours after orally administered tetracyclines. Tetracycline absorption may be reduced as tetracycline antibiotics can chelate with divalent or trivalent cations.
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: (Moderate) Administer oral magnesium-containing products at least 3 hours before or 3 hours after orally administered tetracyclines. Tetracycline absorption may be reduced as tetracycline antibiotics can chelate with divalent or trivalent cations.
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: (Moderate) Administer oral magnesium-containing products at least 3 hours before or 3 hours after orally administered tetracyclines. Tetracycline absorption may be reduced as tetracycline antibiotics can chelate with divalent or trivalent cations.
Methotrexate: (Moderate) Monitor for methotrexate-related adverse reactions during concomitant tetracyclines use. Tetracyclines may decrease intestinal absorption of methotrexate or interfere with the enterohepatic circulation by inhibiting bowel flora and suppressing metabolism of methotrexate by bacteria.
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.
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: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
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 Acetate; Ethinyl Estradiol; Ferrous fumarate: (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. (Moderate) Separate administration of tetracyclines and iron by 2 to 3 hours. Iron may decrease the oral bioavailability of tetracyclines.
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) 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. (Moderate) Separate administration of tetracyclines and iron by 2 to 3 hours. Iron may decrease the oral bioavailability of tetracyclines.
Norgestimate; 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.
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: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
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: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
Palovarotene: (Major) Avoid concomitant use of palovarotene and tetracyclines due to an increased risk for intracranial hypertension. Both tetracyclines and retinoids have been associated with this adverse effect and concomitant use may increase risk.
Pancuronium: (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.
Penicillin G Benzathine: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
Penicillin G Benzathine; Penicillin G Procaine: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
Penicillin G Procaine: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
Penicillin G: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
Penicillin V: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
Penicillins: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
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; Tazobactam: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
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) Separate administration of tetracyclines and iron by 2 to 3 hours. Iron may decrease the oral bioavailability of tetracyclines.
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: (Moderate) 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.
Quinapril; Hydrochlorothiazide, HCTZ: (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.
Rocuronium: (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.
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) Separate administration of tetracyclines and iron by 2 to 3 hours. Iron may decrease the oral bioavailability of tetracyclines.
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: (Moderate) Administer oral magnesium-containing products at least 3 hours before or 3 hours after orally administered tetracyclines. Tetracycline absorption may be reduced as tetracycline antibiotics can chelate with divalent or trivalent cations.
Succinylcholine: (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.
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.
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.
Tretinoin, ATRA: (Major) Avoid the concomitant use of tretinoin 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.
Vecuronium: (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.
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.
Vonoprazan; Amoxicillin: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
Vonoprazan; Amoxicillin; Clarithromycin: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
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.
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 susceptibility interpretive criteria for tetracycline are delineated by pathogen. The MICs are defined for Enterobacterales, Enterococcus sp., Acinetobacter sp., Staphylococcus sp., anaerobes, C. jejuni/coli, Vibrio sp., Bacillus sp. (excluding B. anthracis), Corynebacterium sp., Aeromonas sp., B. mallei, B. pseudomallei, Y. pestis, and other non-Enterobacterales as susceptible at 4 mcg/mL or less, intermediate at 8 mcg/mL, and resistant at 16 mcg/mL or more. The MICs are defined for beta-hemolytic Streptococcus sp., Streptococcus sp. Viridans group, H. influenzae, H. parainfluenzae, M. catarrhalis, Aerococcus sp., Lactococcus sp., Aggregatibacter sp., Cardiobacterium sp., E. corrodens, Kingella sp., and M. catarrhalis as susceptible at 2 mcg/mL or less, intermediate at 4 mcg/mL, and resistant at 8 mcg/mL or more. The MICs are defined for S. pneumoniae as susceptible at 1 mcg/mL or less, intermediate at 2 mcg/mL, and resistant at 4 mcg/mL or more. The MICs are defined for N. gonorrhoeae as susceptible at 0.25 mcg/mL or less, intermediate at 0.5 mcg/mL, and resistant at 2 mcg/mL or more. The MICs are defined for Pasteurella sp., B. anthracis, and Brucella sp. as susceptible at 1 mcg/mL or less. The MICs are defined for F. tularensis as susceptible at 4 mcg/mL or less.
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.
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.
-Route-Specific Pharmacokinetics
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).
-Special Populations
Renal Impairment
The serum half-life of tetracycline hydrochloride is greatly increased in patients with severely impaired renal function.