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  • CLASSES

    Natural and Semi-Synthetic Tetracycline Antibiotics

    DEA CLASS

    Rx

    DESCRIPTION

    Tetracycline antibiotic with activity similar to the other tetracyclines. Main clinical use is for inappropriate secretion of ADH due to its ability to produce nephrogenic diabetes insipidus. Photosensitivity is more frequent and more severe with demeclocycline than with other tetracyclines.

    COMMON BRAND NAMES

    Declomycin

    HOW SUPPLIED

    Declomycin/Demeclocycline/Demeclocycline Hydrochloride Oral Tab: 150mg, 300mg

    DOSAGE & INDICATIONS

    For the treatment of cholera caused by Vibrio cholerae.
    Oral dosage
    Adults

    150 mg PO every 6 hours, or 300 mg PO every 12 hours.

    Children >= 8 years and Adolescents

    7 to 13 mg/kg PO per day in 2 to 4 divided doses. Not to exceed adult doses.

    For the treatment of Campylobacter fetus infections.
    Oral dosage
    Adults

    150 mg PO every 6 hours, or 300 mg PO every 12 hours.

    Children >= 8 years and Adolescents

    7 to 13 mg/kg PO per day in 2 to 4 divided doses. Not to exceed adult doses.

    For the treatment of clostridial diseases caused by Clostridium sp..
    Oral dosage
    Adults

    150 mg PO every 6 hours, or 300 mg PO every 12 hours.

    Children >= 8 years and Adolescents

    7 to 13 mg/kg PO per day in 2 to 4 divided doses. Not to exceed adult doses.

    For the treatment of acute intestinal amebiasis as an adjunct to amebicides.
    Oral dosage
    Adults

    150 mg PO every 6 hours, or 300 mg PO every 12 hours.

    Children >= 8 years and Adolescents

    7 to 13 mg/kg PO per day in 2 to 4 divided doses. Not to exceed adult doses.

    For the treatment of severe acne (i.e. acne vulgaris) as adjunctive therapy.
    Oral dosage
    Adults

    150 mg PO every 6 hours, or 300 mg PO every 12 hours.

    Children >= 8 years and Adolescents

    7 to 13 mg/kg PO per day in 2 to 4 divided doses. Not to exceed adult doses.

    For the treatment of necrotizing ulcerative gingivitis (Fusospirochetosis or Vincent's infection).
    Oral dosage
    Adults

    150 mg PO every 6 hours, or 300 mg PO every 12 hours.

    Children >= 8 years and Adolescents

    7 to 13 mg/kg PO per day in 2 to 4 divided doses. Not to exceed adult doses.

    For the treatment of syphilis (Treponema pallidum) or yaws (Treponema pertenue) when other more effective agents are contraindicated.
    Oral dosage
    Adults

    Not recommended by guidelines. FDA approved dosage is 150 mg PO every 6 hours or 300 mg PO every 12 hours.

    Children and Adolescents 9 to 17 years

    Not recommended by guidelines. FDA approved dosage is 7 to 13 mg/kg/day (Max: 600 mg/day) PO divided 2 to 4 times daily.

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

    150 mg PO every 6 hours, or 300 mg PO every 12 hours.

    Children >= 8 years and Adolescents

    7 to 13 mg/kg PO per day in 2 to 4 divided doses. Not to exceed adult doses.

    For the treatment of bacterial urinary tract infection (UTI) caused by Klebsiella sp., E. coli†, Enterobacter aerogenes†, or Proteus sp..
    Oral dosage
    Adults

    150 mg PO every 6 hours, or 300 mg PO every 12 hours.

    Children >= 8 years and Adolescents

    7 to 13 mg/kg PO per day in 2 to 4 divided doses. Not to exceed adult doses.

    For the treatment of anthrax due to Bacillus anthracis when other more effective agents are contraindicated.
    Oral dosage
    Adults

    150 mg PO every 6 hours or 300 mg PO every 12 hours.

    Children and Adolescents 8 to 17 years

    7 to 13 mg/kg/day PO in 2 to 4 divided doses (Max: 600 mg/day).

    For the treatment of actinomycosis due to Actinomyces israelii when other more effective agents are contraindicated.
    Oral dosage
    Adults

    150 mg PO every 6 hours, or 300 mg PO every 12 hours.

    Children >= 8 years and Adolescents

    7 to 13 mg/kg PO per day in 2 to 4 divided doses. Not to exceed adult doses.

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

    150 mg PO every 6 hours, or 300 mg PO every 12 hours.

    Children >= 8 years and Adolescents

    7 to 13 mg/kg PO per day in 2 to 4 divided doses. Not to exceed adult doses.

    For the treatment of brucellosis due to Brucella sp. in conjunction with spectinomycin.
    Oral dosage
    Adults

    150 mg PO every 6 hours, or 300 mg PO every 12 hours.

    Children >= 8 years and Adolescents

    7 to 13 mg/kg PO per day in 2 to 4 divided doses. Not to exceed adult doses.

    For the treatment of chancroid due to Haemophilus ducreyi.
    Oral dosage
    Adults

    Not recommended by guidelines. FDA-approved dosage is 150 mg PO every 6 hours or 300 mg PO every 12 hours.

    Children and Adolescents 9 to 17 years

    Not recommended by guidelines. FDA-approved dosage is 7 to 13 mg/kg/day (Max: 600 mg/day) PO divided 2 to 4 times daily.

    For the treatment of uncomplicated gonorrhea, including rectal infections in females, cervicitis, and urethritis.
    Oral dosage
    Adults

    Not recommended by guidelines. FDA-approved dosage is 600 mg PO once, then 300 mg PO every 12 hours for 4 days.

    For the treatment of granuloma inguinale (Donovanosis).
    Oral dosage
    Adults

    Not recommended by guidelines. FDA-approved dosage is 150 mg PO every 6 hours or 300 mg PO every 12 hours.

    Children and Adolescents 9 to 17 years

    Not recommended by guidelines. FDA-approved dose is 7 to 13 mg/kg/day (Max: 600 mg/day) PO divided 2 to 4 times daily.

    For the treatment of listeriosis caused by Listeria monocytogenes when other more effective agents are contraindicated.
    Oral dosage
    Adults

    150 mg PO every 6 hours, or 300 mg PO every 12 hours.

    Children >= 8 years and Adolescents

    7 to 13 mg/kg PO per day in 2 to 4 divided doses. Not to exceed adult doses.

    For the treatment of plague following exposure to Yersinia pestis.
    NOTE: The treatment of choice for plague is streptomycin when treating an individual patient or in a contained-casualty setting, and is doxycycline in a mass casualty setting. The risk of serious infection following plague exposure supports the use of demeclocycline if antibiotic susceptibility testing, exhaustion of drug supplies, or allergic reactions preclude the preferred agents.
    Oral dosage
    Adults

    150 mg PO every 6 hours or 300 mg PO every 12 hours for 10 days.

    Children >= 8 years and Adolescents

    7 to 13 mg/kg, not to exceed 600 mg PO per day in 2 to 4 divided doses for 10 days.

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

    150 mg PO every 6 hours, or 300 mg PO every 12 hours.

    Children >= 8 years and Adolescents

    7 to 13 mg/kg PO per day in 2 to 4 divided doses. Not to exceed adult doses.

    For the treatment of Rickettsial infections (e.g. Q fever, Rickettsial pox, Rocky Mountain spotted fever, relapsing fever) including endemic murine typhus.
    Oral dosage
    Adults

    150 mg PO every 6 hours, or 300 mg PO every 12 hours.

    Children >= 8 years and Adolescents

    7 to 13 mg/kg PO per day in 2 to 4 divided doses. Not to exceed adult doses.

    For the treatment of skin and skin structure infections due to susceptible strains of Escherichia coli†, Proteus sp.†, Staphylococcus aureus, Staphylococcus epidermidis†, Streptococcus pneumoniae, or Streptococcus pyogenes†.
    NOTE: Tetracyclines are not the drugs of choice in the treatment of any type of staphylococcal infection.
    Oral dosage
    Adults

    150 mg PO every 6 hours, or 300 mg PO every 12 hours.

    Children >= 8 years and Adolescents

    7 to 13 mg/kg PO per day in 2 to 4 divided doses. Not to exceed adult doses.

    For the treatment of tularemia† following exposure to Francisella tularensis.
    NOTE: The treatment of choice for tularemia is streptomycin when treating an individual patient or in a contained casualty setting, and is doxycycline in a mass casualty setting. The risk of serious infection following tularemia exposure supports the use of demeclocycline if antibiotic susceptibility testing, exhaustion of drug supplies, or allergic reactions preclude the preferred agents.
    Oral dosage
    Adults

    150 mg PO every 6 hours or 300 mg PO every 12 hours for 10 to 14 days.

    Children >= 8 years and Adolescents

    7 to 13 mg/kg (not to exceed 600 mg) PO per day, given in 2 to 4 divided doses, for 10 to 14 days.

    For the treatment of psittacosis.
    Oral dosage
    Adults

    150 mg PO every 6 hours or 300 mg PO every 12 hours.

    Children and Adolescents 9 to 17 years

    7 to 13 mg/kg/day (Max: 600 mg/day) PO divided 2 to 4 times daily.

    For the treatment of non-gonococcal urethritis (NGU) and chlamydia infection, including trachoma and chlamydial conjunctivitis.
    Oral dosage
    Adults

    Not recommended by guidelines. The FDA-approved dosage is 150 mg PO every 6 hours or 300 mg PO every 12 hours.

    Children and Adolescents 9 to 17 years

    Not recommended by guidelines. The FDA-approved dosage is 7 to 13 mg/kg/day (Max: 600 mg/day) PO divided 2 to 4 times daily.

    For the treatment of lymphogranuloma venereum.
    Oral dosage
    Adults

    Not recommended by guidelines. The FDA-approved dosage is 150 mg PO every 6 hours or 300 mg PO every 12 hours.

    Children and Adolescents 9 to 17 years

    Not recommended by guidelines. The FDA-approved dosage is 7 to 13 mg/kg/day (Max: 600 mg/day) PO divided 2 to 4 times daily.

    For the treatment of hyponatremia† in patients with syndrome of inappropriate antidiuretic hormone secretion (SIADH†).
    Oral dosage
    Adults

    600 to 1,200 mg/day PO in 2 to 4 divided doses.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    1.2 g/day PO for SIADH.

    Geriatric

    1.2 g/day PO for SIADH.

    Adolescents

    13 mg/kg/day (Max: 600 mg/day) PO.

    Children

    8 to 12 years: 13 mg/kg/day (Max: 600 mg/day) PO.
    1 to 7 years: Safety and efficacy have not been established.

    Infants

    Safety and efficacy have not been established.

    Neonates

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Lower dosages should be used in patients with preexisting hepatic impairment. Demeclocycline hepatic metabolism may be delayed and elimination half-life extended. Dosage should be modified based on clinical response and degree of hepatic impairment, but no quantitative recommendations are available. Hepatic function tests should be performed prior to and during therapy. Avoid concomitant use other potentially hepatotoxic drugs. If therapy is prolonged, serum concentrations should be monitored.

    Renal Impairment

    Lower dosages should be used in patients with preexisting renal impairment. Dosage should be modified based on clinical response and degree of renal impairment, but no quantitative recommendations are available. Renal function tests should be performed prior to and during therapy. If therapy is prolonged, serum concentrations should be monitored.

    ADMINISTRATION

    For storage information, see specific product information within the How Supplied section.

    Oral Administration

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

    STORAGE

    Declomycin:
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    Tetracyclines hypersensitivity

    Demeclocycline and other tetracycline antibiotics are contraindicated in patients with known tetracyclines hypersensitivity.

    Pregnancy

    Demeclocycline is classified as FDA pregnancy category D. Tetracyclines have been noted to have a detrimental effect on the skeletal development and bone growth of the fetus; only use tetracyclines during pregnancy, especially during the second half of pregnancy, if benefits from treatment outweigh the risks. 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.

    Children, infants, neonates

    Tetracyclines such as demeclocycline, also have a serious effect on the dentin and enamel of developing teeth, causing permanent yellow or brown discoloration and enamel hypoplasia. Except when other therapy is ineffective, use in neonates, infants, and children up to the age of 8 years should be avoided, or the permanent teeth and bone development can be affected.

    Breast-feeding

    Tetracyclines are distributed in small amounts into breast milk. In general, the manufacturers recommend that tetracycline antibiotics, including demeclocycline, not be used in breast-feeding mothers due to a theoretical risk of 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. Demeclocycline does not have a listed American Academy of Pediatrics (AAP) breast-feeding category, but another tetracycline antibiotic, tetracycline, is rated as usually compatible with breast-feeding.  Doxycycline may may be a potential alternative to consider during breast-feeding. However, site of infection, patient factors, local susceptibility patterns, and specific microbial susceptibility should be assessed before choosing an alternative agent. Although doxycyline has also not been evaluated by the AAP, data indicate that after doses of 100 to 200 mg PO, milk concentrations do not exceed an average of 1.8 mg/L. Based on breast milk concentrations after doxycycline doses of 100 mg/day, the estimated average intake of an exclusively breast-fed infant would be about 6% of the maternal weight-adjusted dosage. Studies of long-term tetracycline use in breast-feeding are lacking. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    Renal disease, renal failure, renal impairment

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

    Hepatic disease

    Dose adjustment may be necessary when prescribing demeclocycline to patients with hepatic disease because hepatic excretion into bile may be delayed and elimination half-life extended.

    Sunlight (UV) exposure

    Any tetracycline can produce photosensitivity reactions from sunlight (UV) exposure, but this risk is greatest with demeclocycline. Photosensitivity reactions are believed to be caused by 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. Demeclocycline should be discontinued at the first sign of erythema.

    Driving or operating machinery

    Demeclocycline can cause dizziness, lightheadedness, vertigo, and blurred vision; therefore, patients should know how they react to the drug before driving or operating machinery.

    C. difficile-associated diarrhea, diarrhea, pseudomembranous colitis

    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 demeclocycline, 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.

    Geriatric

    In general, demeclocycline dose selection for the 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 (LTCFs). 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.

    ADVERSE REACTIONS

    Severe

    esophageal ulceration / Delayed / 0-1.0
    Stevens-Johnson syndrome / Delayed / 0-1.0
    anaphylactoid reactions / Rapid / 0-1.0
    angioedema / Rapid / 0-1.0
    increased intracranial pressure / Early / Incidence not known
    pancreatitis / Delayed / Incidence not known
    enterocolitis / Delayed / Incidence not known
    C. difficile-associated diarrhea / Delayed / Incidence not known
    erythema multiforme / Delayed / Incidence not known
    pericarditis / Delayed / Incidence not known
    eosinophilic pneumonia / Delayed / Incidence not known
    lupus-like symptoms / Delayed / Incidence not known
    teratogenesis / Delayed / Incidence not known
    hemolytic anemia / Delayed / Incidence not known
    diabetes insipidus / Delayed / Incidence not known
    azotemia / Delayed / Incidence not known
    renal failure (unspecified) / Delayed / Incidence not known

    Moderate

    myasthenia / Delayed / 0-1.0
    hepatitis / Delayed / 0-1.0
    esophagitis / Delayed / 0-1.0
    elevated hepatic enzymes / Delayed / 0-1.0
    pseudotumor cerebri / Delayed / Incidence not known
    dysphagia / Delayed / Incidence not known
    glossitis / Early / Incidence not known
    pseudomembranous colitis / Delayed / Incidence not known
    superinfection / Delayed / Incidence not known
    candidiasis / Delayed / Incidence not known
    enamel hypoplasia / Delayed / Incidence not known
    thrombocytopenia / Delayed / Incidence not known
    eosinophilia / Delayed / Incidence not known
    neutropenia / Delayed / Incidence not known

    Mild

    dizziness / Early / Incidence not known
    tinnitus / Delayed / Incidence not known
    headache / Early / Incidence not known
    vomiting / Early / Incidence not known
    diarrhea / Early / Incidence not known
    nausea / Early / Incidence not known
    anorexia / Delayed / Incidence not known
    urticaria / Rapid / Incidence not known
    maculopapular rash / Early / Incidence not known
    arthralgia / Delayed / Incidence not known
    skin hyperpigmentation / Delayed / Incidence not known
    photosensitivity / Delayed / Incidence not known
    tooth discoloration / Delayed / Incidence not known
    polydipsia / Early / Incidence not known
    polyuria / Early / Incidence not known
    Jarisch-Herxheimer reaction / Early / Incidence not known

    DRUG INTERACTIONS

    Acitretin: (Contraindicated) The concomitant use of acitretin and systemic tetracyclines is contraindicated, due to the potential for increased cranial pressure and an increased risk of pseudotumor cerebri (benign intracranial hypertension). Pseudotumor cerebri has been reported with systemic retinoid use alone and early signs and symptoms include papilledema, headache, nausea, vomiting and visual disturbances.
    Aluminum Hydroxide: (Moderate) Separate administration of demeclocycline and antacids by 2 to 3 hours. Coadministration may impair absorption of demeclocycline which may decrease its efficacy.
    Aluminum Hydroxide; Magnesium Carbonate: (Moderate) Separate administration of demeclocycline and antacids by 2 to 3 hours. Coadministration may impair absorption of demeclocycline which may decrease its efficacy.
    Aluminum Hydroxide; Magnesium Hydroxide: (Moderate) Separate administration of demeclocycline and antacids by 2 to 3 hours. Coadministration may impair absorption of demeclocycline which may decrease its efficacy.
    Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Moderate) Separate administration of demeclocycline and antacids by 2 to 3 hours. Coadministration may impair absorption of demeclocycline which may decrease its efficacy.
    Aluminum Hydroxide; Magnesium Trisilicate: (Moderate) Separate administration of demeclocycline and antacids by 2 to 3 hours. Coadministration may impair absorption of demeclocycline which may decrease its efficacy.
    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 demeclocycline and antacids by 2 to 3 hours. Coadministration may impair absorption of demeclocycline 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.
    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; Risedronate: (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.
    Carbenicillin: (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.
    Carbetapentane; Guaifenesin; Phenylephrine: (Major) Concurrent administration of oral zinc salts with oral tetracyclines can decrease the absorption of these antiinfectives and possibly interfere with their therapeutic response. This is a result of the formation of insoluble chelates between zinc and the antiinfective. Oral zinc supplements should be administered at least 6 hours before or 2 hours after administering tetracyclines.
    Carbetapentane; Phenylephrine: (Major) Concurrent administration of oral zinc salts with oral tetracyclines can decrease the absorption of these antiinfectives and possibly interfere with their therapeutic response. This is a result of the formation of insoluble chelates between zinc and the antiinfective. Oral zinc supplements should be administered at least 6 hours before or 2 hours after administering tetracyclines.
    Chlorpheniramine; Pseudoephedrine: (Major) Concurrent administration of oral zinc salts with oral tetracyclines can decrease the absorption of these antiinfectives and possibly interfere with their therapeutic response. This is a result of the formation of insoluble chelates between zinc and the antiinfective. Oral zinc supplements should be administered at least 6 hours before or 2 hours after administering tetracyclines.
    Cholera Vaccine: (Major) Avoid the live cholera vaccine in patients that have received demeclocycline within 14 days prior to vaccination. Concurrent administration of the live cholera vaccine with antibiotics active against cholera, such as demeclocycline, 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.
    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.
    Desmopressin: (Major) The antidiuretic response to desmopressin or vasopressin (ADH) may be reduced in patients concomitantly receiving demeclocycline. Caution should be used when coadministering these agents.
    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 a tetracycline to digoxin therapy has been reported to increase the serum digoxin concentration by 100%. Digoxin toxicity has been reported in patients previously stabilized on digoxin who receive antibiotics that affect E. lentum, such as tetracyclines. Other antibiotics that have activity against E. lentum may produce similar effects on digoxin metabolism.
    Drospirenone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Drospirenone; Estetrol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Drospirenone; Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Drospirenone; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Elagolix; Estradiol; Norethindrone acetate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Estradiol Cypionate; Medroxyprogesterone: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Estradiol: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Estradiol; Levonorgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Estradiol; Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Estradiol; Norgestimate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Ethinyl Estradiol; Norelgestromin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Ethinyl Estradiol; Norethindrone Acetate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Ethinyl Estradiol; 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 demeclocycline and impair absorption. Administer demeclocycline 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 demeclocycline and impair absorption. Administer demeclocycline at least one hour prior to or two hours after a meal and/or milk.
    Halobetasol; Tazarotene: (Moderate) The manufacturer states that tazarotene should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as tetracyclines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Heparin: (Minor) Tetracyclines may partially counteract the anticoagulant actions of heparin, according to the product labels. However, this interaction is not likely of clinical significance in most patients since heparin therapy is adjusted to the partial thromboplastin time (aPTT) and other clinical parameters of the patient.
    Hetastarch; Dextrose; Electrolytes: (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. (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.
    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.
    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 demeclocycline and antacids by 2 to 3 hours. Coadministration may impair absorption of demeclocycline 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.
    Mestranol; Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Methotrexate: (Moderate) Oral antibiotics such as tetracyclines may decrease intestinal absorption of methotrexate or interfere with enterohepatic circulation by inhibiting bowel flora and suppressing metabolism of the drug by bacteria. Tetracyclines may displace methotrexate from protein binding sites leading to increased methotrexate levels. A case report describes a patient who received oral doxycycline in combination with her eleventh course of high-dose methotrexate. Methotrexate serum concentrations indicated a prolonged half-life and the patient developed severe gastrointestinal toxicity and myelosuppression including neutropenic fever. This resulted in two prolonged hospital stays and a delay in her next course of chemotherapy.
    Methoxsalen: (Moderate) Use methoxsalen and tetracyclines together with caution; the risk of severe burns/photosensitivity may be additive. If concurrent use is necessary, closely monitor patients for signs or symptoms of skin toxicity.
    Mipomersen: (Moderate) Caution should be exercised when mipomersen is used with other medications known to have potential for hepatotoxicity, such as tetracyclines. The effect of concomitant administration of mipomersen with other hepatotoxic medications is unknown. More frequent monitoring of liver-related tests may be warranted.
    Molindone: (Major) The tablet formulation of molindone contains calcium sulfate as an excipient and the calcium ions may interfere with the absorption of tetracyclines. It may be advisable to consider an alternative to tetracycline treatment during molindone administration.
    Nafcillin: (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.
    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: (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.
    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.
    Relugolix; Estradiol; Norethindrone acetate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Segesterone Acetate; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Sodium Bicarbonate: (Major) Early reports noted an increase in the excretion of tetracyclines during coadministration with sodium bicarbonate, and that the oral absorption of tetracyclines is reduced by sodium bicarbonate via increased gastric pH. However, conflicting data have been reported, and further study is needed. Two recent studies show no effect of oral sodium bicarbonate administration on tetracycline oral bioavailability. In one of these trials, coadministration with sodium bicarbonate was reported to have no effect on tetracycline urinary excretion, Cmax, or AUC. Until more information is available, avoid simultaneous administration of sodium bicarbonate and tetracyclines. When concurrent therapy is needed, stagger administration times by several hours to minimize the potential for interaction, and monitor for antimicrobial efficacy.
    Sodium Ferric Gluconate Complex; ferric pyrophosphate citrate: (Moderate) 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.
    St. John's Wort, Hypericum perforatum: (Moderate) St. John's Wort is known to cause photosensitivity. In theory it is possible that additive photosensitizing effects may result from the concomitant use of St. John's Wort with other photosensitizing drugs such as tetracyclines.
    Sucralfate: (Moderate) Sucralfate should be given 2 hours before or after the oral administration of tetracyclines. Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain aluminum salts, calcium salts, iron salts, magnesium salts, and/or zinc salts. Sucralfate, because it contains aluminum in its structure and due to its mechanism of action, can bind with tetracyclines in the GI tract, reducing the bioavailability of these agents.
    Sulfonylureas: (Moderate) Additive photosensitization may be seen with concurrent administration of sulfonylureas and other photosensitizing agents including tetracyclines. Prevention of photosensitivity includes adequate protection from sources of UV radiation (e.g., avoiding sun exposure and tanning booths) and the use of protective clothing and sunscreens on exposed skin.
    Tazarotene: (Moderate) The manufacturer states that tazarotene should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as tetracyclines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Ticarcillin: (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.
    Ticarcillin; 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.
    Tretinoin, ATRA: (Major) The concomitant use of systemic tretinoin, ATRA and systemic tetracyclines should be avoided due to the potential for increased intracranial pressure and an increased risk of pseudotumor cerebri (benign intracranial hypertension). Pseudotumor cerebri has been reported with systemic retinoid use alone and early signs and symptoms include papilledema, headache, nausea, vomiting and visual disturbances. In addition, a manufacturer of topical tretinoin states that tretinoin, ATRA should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as tetracyclines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
    Vasopressin, ADH: (Moderate) Monitor hemodynamics and adjust the dose of vasopressin as needed when used concomitantly with drugs suspected of causing diabetes insipidus, such as demeclocycline. Use together may decrease the pressor and antidiuretic effects of vasopressin.
    Verteporfin: (Moderate) Use caution if coadministration of verteporfin with tetracyclines is necessary due to the risk of increased photosensitivity. Verteporfin is a light-activated drug used in photodynamic therapy; all patients treated with verteporfin will be photosensitive. Concomitant use of other photosensitizing agents like tetracyclines may increase the risk of a photosensitivity reaction.
    Warfarin: (Moderate) Tetracyclines may increase the action of warfarin and other oral anticoagulants by either impairing prothrombin utilization or, possibly, decreasing production of vitamin K because of its antiinfective action on gut bacteria. Monitor patients for signs and symptoms of bleeding. Additionally, increased monitoring of the INR, especially during initiation and upon discontinuation of the antibiotic, may be necessary.
    Zinc Salts: (Major) Concurrent administration of oral zinc salts with oral tetracyclines can decrease the absorption of these antiinfectives and possibly interfere with their therapeutic response. This is a result of the formation of insoluble chelates between zinc and the antiinfective. Oral zinc supplements should be administered at least 6 hours before or 2 hours after administering tetracyclines.
    Zinc: (Major) Concurrent administration of oral zinc salts with oral tetracyclines can decrease the absorption of these antiinfectives and possibly interfere with their therapeutic response. This is a result of the formation of insoluble chelates between zinc and the antiinfective. Oral zinc supplements should be administered at least 6 hours before or 2 hours after administering tetracyclines.

    PREGNANCY AND LACTATION

    Pregnancy

    Demeclocycline is classified as FDA pregnancy category D. Tetracyclines have been noted to have a detrimental effect on the skeletal development and bone growth of the fetus; only use tetracyclines during pregnancy, especially during the second half of pregnancy, if benefits from treatment outweigh the risks. 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.

    Tetracyclines are distributed in small amounts into breast milk. In general, the manufacturers recommend that tetracycline antibiotics, including demeclocycline, not be used in breast-feeding mothers due to a theoretical risk of 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. Demeclocycline does not have a listed American Academy of Pediatrics (AAP) breast-feeding category, but another tetracycline antibiotic, tetracycline, is rated as usually compatible with breast-feeding.  Doxycycline may may be a potential alternative to consider during breast-feeding. However, site of infection, patient factors, local susceptibility patterns, and specific microbial susceptibility should be assessed before choosing an alternative agent. Although doxycyline has also not been evaluated by the AAP, data indicate that after doses of 100 to 200 mg PO, milk concentrations do not exceed an average of 1.8 mg/L. Based on breast milk concentrations after doxycycline doses of 100 mg/day, the estimated average intake of an exclusively breast-fed infant would be about 6% of the maternal weight-adjusted dosage. Studies of long-term tetracycline use in breast-feeding are lacking. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    Tetracyclines can be bacteriostatic or bactericidal depending on the concentration at the site of action or the organism being treated. In gram-negative bacteria, transportation of the tetracycline into the cell occurs both by passive diffusion and through an energy-dependent active transport system that pumps all tetracyclines through the inner cytoplasmic membrane. The latter system is also thought to exist in gram-positive bacteria. Binding of demeclocycline blocks the binding of aminoacyl transfer RNA (tRNA) to the messenger RNA (mRNA). Bacterial protein synthesis is inhibited, which ultimately accounts for the antibacterial action. In mammalian cells, high concentrations of antibiotic also can interfere with protein synthesis, but these cells lack the active transport systems found in bacteria. Resistance develops when the bacterial cell mutates and the cell wall becomes less permeable. With the exception of minocycline, there is almost complete cross-resistance among the tetracyclines.
     
    Demeclocycline is the only tetracycline that is used in the treatment of SIADH. Demeclocycline produces a nephrogenic diabetes insipidus. Diuresis is produced by inhibition of ADH-induced water reabsorption in the distal portion of the convoluted tubules and collecting ducts of the kidneys. These effects are seen within 5 days and are reversed within 2—6 days following cessation of therapy. Many clinicians prefer demeclocycline over lithium for this condition due to demeclocycline's lower risk of toxicity.

    PHARMACOKINETICS

    Demeclocycline is administered orally. Peak serum concentrations are achieved in 3—4 hours. Demeclocycline is distributed widely into body fluids, including slow accumulation in the CSF. All tetracyclines tend to concentrate in bone, liver, tumors, spleen, and teeth. They cross the placenta and are distributed into breast milk. Protein binding ranges from 65—90%.
     
    Demeclocycline undergoes 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 with parenteral administration because of enterohepatic circulation. The primary excretion route is the kidney. Serum half-life is estimated to be about 10—17 hours in adults with normal renal function. About 42% of a dose is excreted unchanged from either route.

    Oral Route

    Absorption of demeclocycline from the GI tract following oral dosing is about 60—80% in the fasting state. Most absorption takes place in the stomach and upper intestine. As the dosage is increased, the percentage absorbed decreases. Chelation with di- and trivalent ions in antacids and dairy products reduces oral absorption.  Peak serum concentrations are achieved in 3—4 hours.